diff --git a/setup.py b/setup.py
index 4aad42e1ea0..8a3e391afbd 100644
--- a/setup.py
+++ b/setup.py
@@ -98,8 +98,6 @@ LICENSE = 'Apache License 2.0'
 CLASSIFIERS = [
     'Development Status :: 5 - Production/Stable',
     'Programming Language :: Python',
-    'Programming Language :: Python :: 2',
-    'Programming Language :: Python :: 2.7',
     'Programming Language :: Python :: 3',
     'Programming Language :: Python :: 3.5',
     'Programming Language :: Python :: 3.6',
diff --git a/src/python/grpcio_admin/setup.py b/src/python/grpcio_admin/setup.py
index 6c2438ef5ee..08f2a6e7dad 100644
--- a/src/python/grpcio_admin/setup.py
+++ b/src/python/grpcio_admin/setup.py
@@ -30,7 +30,6 @@ import grpc_version
 CLASSIFIERS = [
     'Development Status :: 5 - Production/Stable',
     'Programming Language :: Python',
-    'Programming Language :: Python :: 2',
     'Programming Language :: Python :: 3',
     'License :: OSI Approved :: Apache Software License',
 ]
diff --git a/src/python/grpcio_channelz/setup.py b/src/python/grpcio_channelz/setup.py
index 678b5ef13f3..1f6450aaba3 100644
--- a/src/python/grpcio_channelz/setup.py
+++ b/src/python/grpcio_channelz/setup.py
@@ -47,8 +47,6 @@ class _NoOpCommand(setuptools.Command):
 CLASSIFIERS = [
     'Development Status :: 5 - Production/Stable',
     'Programming Language :: Python',
-    'Programming Language :: Python :: 2',
-    'Programming Language :: Python :: 2.7',
     'Programming Language :: Python :: 3',
     'Programming Language :: Python :: 3.4',
     'Programming Language :: Python :: 3.5',
diff --git a/src/python/grpcio_csds/setup.py b/src/python/grpcio_csds/setup.py
index c699fc7d921..e0eb60a2de6 100644
--- a/src/python/grpcio_csds/setup.py
+++ b/src/python/grpcio_csds/setup.py
@@ -30,7 +30,6 @@ import grpc_version
 CLASSIFIERS = [
     'Development Status :: 5 - Production/Stable',
     'Programming Language :: Python',
-    'Programming Language :: Python :: 2',
     'Programming Language :: Python :: 3',
     'License :: OSI Approved :: Apache Software License',
 ]
diff --git a/src/python/grpcio_health_checking/setup.py b/src/python/grpcio_health_checking/setup.py
index fa1fbbd55ad..d9d1f201ae6 100644
--- a/src/python/grpcio_health_checking/setup.py
+++ b/src/python/grpcio_health_checking/setup.py
@@ -46,8 +46,6 @@ class _NoOpCommand(setuptools.Command):
 CLASSIFIERS = [
     'Development Status :: 5 - Production/Stable',
     'Programming Language :: Python',
-    'Programming Language :: Python :: 2',
-    'Programming Language :: Python :: 2.7',
     'Programming Language :: Python :: 3',
     'Programming Language :: Python :: 3.4',
     'Programming Language :: Python :: 3.5',
diff --git a/src/python/grpcio_reflection/setup.py b/src/python/grpcio_reflection/setup.py
index 2d0a3fcdaaf..6c44800e924 100644
--- a/src/python/grpcio_reflection/setup.py
+++ b/src/python/grpcio_reflection/setup.py
@@ -47,8 +47,6 @@ class _NoOpCommand(setuptools.Command):
 CLASSIFIERS = [
     'Development Status :: 5 - Production/Stable',
     'Programming Language :: Python',
-    'Programming Language :: Python :: 2',
-    'Programming Language :: Python :: 2.7',
     'Programming Language :: Python :: 3',
     'Programming Language :: Python :: 3.4',
     'Programming Language :: Python :: 3.5',
diff --git a/src/python/grpcio_status/setup.py b/src/python/grpcio_status/setup.py
index eb49069c34f..762023149a4 100644
--- a/src/python/grpcio_status/setup.py
+++ b/src/python/grpcio_status/setup.py
@@ -46,8 +46,6 @@ class _NoOpCommand(setuptools.Command):
 CLASSIFIERS = [
     'Development Status :: 5 - Production/Stable',
     'Programming Language :: Python',
-    'Programming Language :: Python :: 2',
-    'Programming Language :: Python :: 2.7',
     'Programming Language :: Python :: 3',
     'Programming Language :: Python :: 3.4',
     'Programming Language :: Python :: 3.5',
diff --git a/test/distrib/python/test_packages.sh b/test/distrib/python/test_packages.sh
index e9f494310d6..a68eba401b2 100755
--- a/test/distrib/python/test_packages.sh
+++ b/test/distrib/python/test_packages.sh
@@ -35,7 +35,7 @@ REFLECTION_ARCHIVES=("$EXTERNAL_GIT_ROOT"/input_artifacts/grpcio-reflection-[0-9
 TESTING_ARCHIVES=("$EXTERNAL_GIT_ROOT"/input_artifacts/grpcio-testing-[0-9]*.tar.gz)
 
 VIRTUAL_ENV=$(mktemp -d)
-virtualenv "$VIRTUAL_ENV"
+python3 -m virtualenv "$VIRTUAL_ENV"
 PYTHON=$VIRTUAL_ENV/bin/python
 "$PYTHON" -m pip install --upgrade six pip wheel
 
diff --git a/tools/distrib/python/grpc_prefixed/templates/setup.py.template b/tools/distrib/python/grpc_prefixed/templates/setup.py.template
index 2d62270d04d..27ae518b99a 100644
--- a/tools/distrib/python/grpc_prefixed/templates/setup.py.template
+++ b/tools/distrib/python/grpc_prefixed/templates/setup.py.template
@@ -20,7 +20,6 @@ import setuptools
 CLASSIFIERS = [
     'Development Status :: 7 - Inactive',
     'Programming Language :: Python',
-    'Programming Language :: Python :: 2',
     'Programming Language :: Python :: 3',
     'License :: OSI Approved :: Apache Software License',
 ]
diff --git a/tools/distrib/python/grpcio_tools/setup.py b/tools/distrib/python/grpcio_tools/setup.py
index c64f77778f4..46b0ad20cdf 100644
--- a/tools/distrib/python/grpcio_tools/setup.py
+++ b/tools/distrib/python/grpcio_tools/setup.py
@@ -55,12 +55,7 @@ _parallel_compile_patch.monkeypatch_compile_maybe()
 CLASSIFIERS = [
     'Development Status :: 5 - Production/Stable',
     'Programming Language :: Python',
-    'Programming Language :: Python :: 2',
-    'Programming Language :: Python :: 2.7',
     'Programming Language :: Python :: 3',
-    'Programming Language :: Python :: 3.4',
-    'Programming Language :: Python :: 3.5',
-    'Programming Language :: Python :: 3.6',
     'License :: OSI Approved :: Apache Software License',
 ]
 
diff --git a/tools/distrib/python/xds_protos/build_validate_upload.sh b/tools/distrib/python/xds_protos/build_validate_upload.sh
index 4218940e7da..00135fcaf06 100755
--- a/tools/distrib/python/xds_protos/build_validate_upload.sh
+++ b/tools/distrib/python/xds_protos/build_validate_upload.sh
@@ -23,21 +23,13 @@ rm -rf ${WORK_DIR}/dist
 
 # Generate the package content then build the source wheel
 python3 build.py
-python3 setup.py sdist
-python2 setup.py bdist_wheel
 python3 setup.py bdist_wheel
 
 # Run the tests to ensure all protos are importable, also avoid confusing normal
 # imports with relative imports
 pushd $(mktemp -d '/tmp/test_xds_protos.XXXXXX')
-python2 -m virtualenv env
-env/bin/python -m pip install ${WORK_DIR}/dist/xds-protos-*.tar.gz
-cp ${WORK_DIR}/generated_file_import_test.py generated_file_import_test.py
-env/bin/python generated_file_import_test.py
-popd
-pushd $(mktemp -d '/tmp/test_xds_protos.XXXXXX')
 python3 -m virtualenv env
-env/bin/python -m pip install ${WORK_DIR}/dist/xds-protos-*.tar.gz
+env/bin/python -m pip install ${WORK_DIR}/dist/*.whl
 cp ${WORK_DIR}/generated_file_import_test.py generated_file_import_test.py
 env/bin/python generated_file_import_test.py
 popd
diff --git a/tools/distrib/python/xds_protos/setup.py b/tools/distrib/python/xds_protos/setup.py
index 2ed04c421a4..5a5e95cff77 100644
--- a/tools/distrib/python/xds_protos/setup.py
+++ b/tools/distrib/python/xds_protos/setup.py
@@ -27,7 +27,6 @@ PACKAGES = setuptools.find_packages(where=".", exclude=EXCLUDE_PYTHON_FILES)
 CLASSIFIERS = [
     'Development Status :: 3 - Alpha',
     'Programming Language :: Python',
-    'Programming Language :: Python :: 2',
     'Programming Language :: Python :: 3',
     'License :: OSI Approved :: Apache Software License',
 ]
@@ -38,7 +37,7 @@ INSTALL_REQUIRES = [
 SETUP_REQUIRES = INSTALL_REQUIRES + ['grpcio-tools']
 setuptools.setup(
     name='xds-protos',
-    version='0.0.8',
+    version='0.0.10',
     packages=PACKAGES,
     description='Generated Python code from envoyproxy/data-plane-api',
     long_description_content_type='text/x-rst',
diff --git a/tools/dockerfile/distribtest/python_arch_x64/Dockerfile b/tools/dockerfile/distribtest/python_arch_x64/Dockerfile
index 9e43d00b410..ed4ff753dab 100644
--- a/tools/dockerfile/distribtest/python_arch_x64/Dockerfile
+++ b/tools/dockerfile/distribtest/python_arch_x64/Dockerfile
@@ -12,10 +12,10 @@
 # See the License for the specific language governing permissions and
 # limitations under the License.
 
-FROM base/archlinux
+FROM archlinux:base
 
 RUN pacman --noconfirm -Syy
 RUN pacman --noconfirm -S openssl
-RUN pacman --noconfirm -S python2
-RUN pacman --noconfirm -S python2-pip
-RUN pip2 install virtualenv
+RUN pacman --noconfirm -S python
+RUN pacman --noconfirm -S python-pip
+RUN pip3 install virtualenv
diff --git a/tools/dockerfile/distribtest/python_centos6_x64/Dockerfile b/tools/dockerfile/distribtest/python_centos6_x64/Dockerfile
deleted file mode 100644
index e71f655796e..00000000000
--- a/tools/dockerfile/distribtest/python_centos6_x64/Dockerfile
+++ /dev/null
@@ -1,33 +0,0 @@
-# Copyright 2015 gRPC authors.
-#
-# Licensed under the Apache License, Version 2.0 (the "License");
-# you may not use this file except in compliance with the License.
-# You may obtain a copy of the License at
-#
-#     http://www.apache.org/licenses/LICENSE-2.0
-#
-# Unless required by applicable law or agreed to in writing, software
-# distributed under the License is distributed on an "AS IS" BASIS,
-# WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
-# See the License for the specific language governing permissions and
-# limitations under the License.
-
-FROM centos:6
-
-RUN yum -y install https://dl.fedoraproject.org/pub/epel/epel-release-latest-6.noarch.rpm
-
-# Vanilla CentOS6 only has python 2.6 and we don't support that.
-RUN yum -y install yum -y install https://centos6.iuscommunity.org/ius-release.rpm
-RUN yum install -y python27
-
-# Override python2.6
-RUN ln -s /usr/bin/python2.7 /usr/local/bin/python
-RUN ln -s /usr/bin/python2.7 /usr/local/bin/python2
-
-# Install pip
-RUN curl https://bootstrap.pypa.io/get-pip.py | python -
-
-# "which" command required by python's run_distrib_test.sh
-RUN yum install -y which
-
-RUN pip install virtualenv
diff --git a/tools/dockerfile/distribtest/python_centos7_x64/Dockerfile b/tools/dockerfile/distribtest/python_centos7_x64/Dockerfile
index 4375a3f69c4..7650b622908 100644
--- a/tools/dockerfile/distribtest/python_centos7_x64/Dockerfile
+++ b/tools/dockerfile/distribtest/python_centos7_x64/Dockerfile
@@ -17,4 +17,5 @@ FROM centos:7
 RUN yum install -y python
 RUN yum install -y epel-release
 RUN yum install -y python-pip
-RUN pip install virtualenv
+RUN yum install -y python3
+RUN python3 -m pip install virtualenv
diff --git a/tools/dockerfile/distribtest/python_dev_alpine3.7_x64/Dockerfile b/tools/dockerfile/distribtest/python_dev_alpine3.7_x64/Dockerfile
index b51cad937b2..0272a2758f5 100644
--- a/tools/dockerfile/distribtest/python_dev_alpine3.7_x64/Dockerfile
+++ b/tools/dockerfile/distribtest/python_dev_alpine3.7_x64/Dockerfile
@@ -14,11 +14,11 @@
 
 FROM alpine:3.11
 
-RUN apk add --update build-base linux-headers python python2-dev py2-pip
+RUN apk add --update build-base linux-headers python3 python3-dev py3-pip
 
-RUN pip install --upgrade pip==19.3.1
+RUN pip3 install --upgrade pip==19.3.1
 
-RUN pip install virtualenv
+RUN pip3 install virtualenv
 
 # bash is required for our test script invocation
 # ideally, we want to fix the invocation mechanism
diff --git a/tools/dockerfile/distribtest/python_dev_arch_x64/Dockerfile b/tools/dockerfile/distribtest/python_dev_arch_x64/Dockerfile
index 7f09fd64234..a24e832493f 100644
--- a/tools/dockerfile/distribtest/python_dev_arch_x64/Dockerfile
+++ b/tools/dockerfile/distribtest/python_dev_arch_x64/Dockerfile
@@ -12,11 +12,11 @@
 # See the License for the specific language governing permissions and
 # limitations under the License.
 
-FROM base/archlinux
+FROM archlinux:base
 
 RUN pacman --noconfirm -Syy
 RUN pacman --noconfirm -S openssl
-RUN pacman --noconfirm -S python2
-RUN pacman --noconfirm -S python2-pip
-RUN pip2 install virtualenv
+RUN pacman --noconfirm -S python
+RUN pacman --noconfirm -S python-pip
+RUN pip3 install virtualenv
 RUN pacman --noconfirm -S base-devel
diff --git a/tools/dockerfile/distribtest/python_dev_centos7_x64/Dockerfile b/tools/dockerfile/distribtest/python_dev_centos7_x64/Dockerfile
index df5ca6489db..b1299af7101 100644
--- a/tools/dockerfile/distribtest/python_dev_centos7_x64/Dockerfile
+++ b/tools/dockerfile/distribtest/python_dev_centos7_x64/Dockerfile
@@ -14,12 +14,12 @@
 
 FROM centos:7
 
-RUN yum install -y python
-RUN yum install -y python-devel
+RUN yum install -y python3
+RUN yum install -y python3-devel
 RUN yum install -y epel-release
-RUN yum install -y python-pip
-RUN pip install --upgrade pip==19.3.1
-RUN pip install -U virtualenv
+RUN yum install -y python3-pip
+RUN pip3 install --upgrade pip==19.3.1
+RUN pip3 install -U virtualenv
 
 # The default gcc of CentOS 7 is gcc 4.8 which is older than gcc 4.9,
 # the minimum supported gcc version for gRPC Core so let's upgrade to
diff --git a/tools/dockerfile/distribtest/python_dev_fedora23_x64/Dockerfile b/tools/dockerfile/distribtest/python_dev_fedora23_x64/Dockerfile
index 0dbf5e4c21a..cfa3d934cb8 100644
--- a/tools/dockerfile/distribtest/python_dev_fedora23_x64/Dockerfile
+++ b/tools/dockerfile/distribtest/python_dev_fedora23_x64/Dockerfile
@@ -14,10 +14,10 @@
 
 FROM fedora:23
 
-RUN yum clean all && yum update -y && yum install -y python python-pip
-RUN pip install virtualenv
+RUN yum clean all && yum update -y && yum install -y python3 python3-pip
+RUN pip3 install virtualenv==16.7.9
 
 RUN yum groupinstall -y "Development Tools"
 RUN yum install -y redhat-rpm-config
 RUN yum install -y gcc-c++
-RUN yum install -y python2-devel
+RUN yum install -y python3-devel
diff --git a/tools/dockerfile/distribtest/python_dev_jessie_x64/Dockerfile b/tools/dockerfile/distribtest/python_dev_jessie_x64/Dockerfile
index c2228989cdc..e4ee142d90c 100644
--- a/tools/dockerfile/distribtest/python_dev_jessie_x64/Dockerfile
+++ b/tools/dockerfile/distribtest/python_dev_jessie_x64/Dockerfile
@@ -14,8 +14,8 @@
 
 FROM debian:jessie
 
-RUN apt-get update && apt-get install -y python python-pip
-RUN pip install virtualenv
+RUN apt-get update && apt-get install -y python3 python3-pip
+RUN pip3 install virtualenv==16.7.9
 
 RUN apt-get install -y build-essential
-RUN apt-get install -y python-dev
+RUN apt-get install -y python3-dev
diff --git a/tools/dockerfile/distribtest/python_dev_jessie_x86/Dockerfile b/tools/dockerfile/distribtest/python_dev_jessie_x86/Dockerfile
index b1d1a31061a..b59e4b4204c 100644
--- a/tools/dockerfile/distribtest/python_dev_jessie_x86/Dockerfile
+++ b/tools/dockerfile/distribtest/python_dev_jessie_x86/Dockerfile
@@ -14,12 +14,12 @@
 
 FROM i386/debian:jessie
 
-RUN apt-get update && apt-get install -y python python-pip
+RUN apt-get update && apt-get install -y python3 python3-pip
 
-RUN pip install virtualenv
+RUN pip3 install virtualenv==16.7.9
 
 RUN apt-get install -y build-essential
-RUN apt-get install -y python-dev
+RUN apt-get install -y python3-dev
 
 # docker is running on a 64-bit machine, so we need to
 # override "uname -m" to report i686 instead of x86_64, otherwise
diff --git a/tools/dockerfile/distribtest/python_dev_ubuntu1604_x64/Dockerfile b/tools/dockerfile/distribtest/python_dev_ubuntu1604_x64/Dockerfile
index 1ff1e0a1d61..1f5775fb99e 100644
--- a/tools/dockerfile/distribtest/python_dev_ubuntu1604_x64/Dockerfile
+++ b/tools/dockerfile/distribtest/python_dev_ubuntu1604_x64/Dockerfile
@@ -14,9 +14,9 @@
 
 FROM ubuntu:16.04
 
-RUN apt-get update -y && apt-get install -y python python-pip
+RUN apt-get update -y && apt-get install -y python3 python3-pip
 
 RUN apt-get install -y build-essential
-RUN apt-get install -y python-dev
+RUN apt-get install -y python3-dev
 
-RUN pip install virtualenv
+RUN pip3 install virtualenv==16.7.9
diff --git a/tools/dockerfile/distribtest/python_dev_ubuntu1804_x64/Dockerfile b/tools/dockerfile/distribtest/python_dev_ubuntu1804_x64/Dockerfile
index a7c48dd23f7..7bcb5830d1f 100644
--- a/tools/dockerfile/distribtest/python_dev_ubuntu1804_x64/Dockerfile
+++ b/tools/dockerfile/distribtest/python_dev_ubuntu1804_x64/Dockerfile
@@ -14,9 +14,9 @@
 
 FROM ubuntu:18.04
 
-RUN apt-get update -y && apt-get install -y python python-pip
+RUN apt-get update -y && apt-get install -y python3 python3-pip
 
 RUN apt-get install -y build-essential
-RUN apt-get install -y python-dev
+RUN apt-get install -y python3-dev
 
-RUN pip install virtualenv
+RUN pip3 install virtualenv
diff --git a/tools/dockerfile/distribtest/python_fedora23_x64/Dockerfile b/tools/dockerfile/distribtest/python_fedora34_x64/Dockerfile
similarity index 83%
rename from tools/dockerfile/distribtest/python_fedora23_x64/Dockerfile
rename to tools/dockerfile/distribtest/python_fedora34_x64/Dockerfile
index 60f788df8b0..158ba778782 100644
--- a/tools/dockerfile/distribtest/python_fedora23_x64/Dockerfile
+++ b/tools/dockerfile/distribtest/python_fedora34_x64/Dockerfile
@@ -12,7 +12,7 @@
 # See the License for the specific language governing permissions and
 # limitations under the License.
 
-FROM fedora:23
+FROM fedora:34
 
-RUN yum clean all && yum update -y && yum install -y python python-pip
-RUN pip install virtualenv
+RUN yum clean all && yum update -y && yum install -y python3 python3-pip
+RUN pip3 install virtualenv
diff --git a/tools/dockerfile/distribtest/python_opensuse_x64/Dockerfile b/tools/dockerfile/distribtest/python_opensuse_x64/Dockerfile
index 4a74fe51217..d8179ef68b4 100644
--- a/tools/dockerfile/distribtest/python_opensuse_x64/Dockerfile
+++ b/tools/dockerfile/distribtest/python_opensuse_x64/Dockerfile
@@ -12,10 +12,10 @@
 # See the License for the specific language governing permissions and
 # limitations under the License.
 
-FROM opensuse:42.1
+FROM opensuse/leap:latest
 
-RUN zypper --non-interactive install python
-RUN zypper --non-interactive install python-pip
+RUN zypper --non-interactive install python3
+RUN zypper --non-interactive install python3-pip
 
 # "which" command required by python's run_distrib_test.sh
 RUN zypper --non-interactive install which
@@ -24,4 +24,4 @@ RUN zypper --non-interactive install which
 # https://pypi.python.org/simple/
 RUN zypper --non-interactive install ca-certificates-mozilla
 
-RUN pip install virtualenv
+RUN pip3 install virtualenv
diff --git a/tools/dockerfile/distribtest/python_jessie_x64/Dockerfile b/tools/dockerfile/distribtest/python_stretch_x64/Dockerfile
similarity index 83%
rename from tools/dockerfile/distribtest/python_jessie_x64/Dockerfile
rename to tools/dockerfile/distribtest/python_stretch_x64/Dockerfile
index 2c8ce8eca26..2b47ad97e28 100644
--- a/tools/dockerfile/distribtest/python_jessie_x64/Dockerfile
+++ b/tools/dockerfile/distribtest/python_stretch_x64/Dockerfile
@@ -12,7 +12,7 @@
 # See the License for the specific language governing permissions and
 # limitations under the License.
 
-FROM debian:jessie
+FROM debian:stretch
 
-RUN apt-get update && apt-get install -y python python-pip
-RUN pip install virtualenv
+RUN apt-get update && apt-get install -y python3 python3-pip
+RUN pip3 install virtualenv==16.7.9
diff --git a/tools/dockerfile/distribtest/python_jessie_x86/Dockerfile b/tools/dockerfile/distribtest/python_stretch_x86/Dockerfile
similarity index 86%
rename from tools/dockerfile/distribtest/python_jessie_x86/Dockerfile
rename to tools/dockerfile/distribtest/python_stretch_x86/Dockerfile
index d5b63421c59..cbeb53baddf 100644
--- a/tools/dockerfile/distribtest/python_jessie_x86/Dockerfile
+++ b/tools/dockerfile/distribtest/python_stretch_x86/Dockerfile
@@ -12,11 +12,11 @@
 # See the License for the specific language governing permissions and
 # limitations under the License.
 
-FROM i386/debian:jessie
+FROM i386/debian:stretch
 
-RUN apt-get update && apt-get install -y python python-pip
+RUN apt-get update && apt-get install -y python3 python3-pip
 
-RUN pip install virtualenv
+RUN pip3 install virtualenv==16.7.9
 
 # docker is running on a 64-bit machine, so we need to
 # override "uname -m" to report i686 instead of x86_64, otherwise
diff --git a/tools/dockerfile/distribtest/python_ubuntu1604_x64/Dockerfile b/tools/dockerfile/distribtest/python_ubuntu1604_x64/Dockerfile
index d00c7b4584a..c8692e11c8b 100644
--- a/tools/dockerfile/distribtest/python_ubuntu1604_x64/Dockerfile
+++ b/tools/dockerfile/distribtest/python_ubuntu1604_x64/Dockerfile
@@ -14,10 +14,10 @@
 
 FROM ubuntu:16.04
 
-RUN apt-get update -y && apt-get install -y python python-pip
+RUN apt-get update -y && apt-get install -y python3 python3-pip
 
 # Necessary to fix virtualenv compatibility problems with python2.7
-RUN pip install --upgrade pip==19.3.1
+RUN pip3 install --upgrade pip==19.3.1
 
 # Ubuntu's python-pip package installs pip to /usr/bin, whereas the upgraded
 # pip lives at /usr/local/bin/pip. We'll use the absolute path for now, since
diff --git a/tools/dockerfile/distribtest/python_ubuntu1804_x64/Dockerfile b/tools/dockerfile/distribtest/python_ubuntu1804_x64/Dockerfile
index ac71663a346..9b1ab18742a 100644
--- a/tools/dockerfile/distribtest/python_ubuntu1804_x64/Dockerfile
+++ b/tools/dockerfile/distribtest/python_ubuntu1804_x64/Dockerfile
@@ -14,6 +14,6 @@
 
 FROM ubuntu:18.04
 
-RUN apt-get update -y && apt-get install -y python python-pip
+RUN apt-get update -y && apt-get install -y python3 python3-pip
 
-RUN pip install virtualenv
+RUN pip3 install virtualenv
diff --git a/tools/run_tests/artifacts/artifact_targets.py b/tools/run_tests/artifacts/artifact_targets.py
index ec9d33e782d..0fa32cf3135 100644
--- a/tools/run_tests/artifacts/artifact_targets.py
+++ b/tools/run_tests/artifacts/artifact_targets.py
@@ -358,15 +358,11 @@ def targets():
         PythonArtifact('manylinux2014', 'x86', 'cp37-cp37m'),
         PythonArtifact('manylinux2014', 'x86', 'cp38-cp38'),
         PythonArtifact('manylinux2014', 'x86', 'cp39-cp39'),
-        PythonArtifact('manylinux2010', 'x64', 'cp27-cp27m'),
-        PythonArtifact('manylinux2010', 'x64', 'cp27-cp27mu'),
         PythonArtifact('manylinux2010', 'x64', 'cp35-cp35m'),
         PythonArtifact('manylinux2010', 'x64', 'cp36-cp36m'),
         PythonArtifact('manylinux2010', 'x64', 'cp37-cp37m'),
         PythonArtifact('manylinux2010', 'x64', 'cp38-cp38'),
         PythonArtifact('manylinux2010', 'x64', 'cp39-cp39'),
-        PythonArtifact('manylinux2010', 'x86', 'cp27-cp27m'),
-        PythonArtifact('manylinux2010', 'x86', 'cp27-cp27mu'),
         PythonArtifact('manylinux2010', 'x86', 'cp35-cp35m'),
         PythonArtifact('manylinux2010', 'x86', 'cp36-cp36m'),
         PythonArtifact('manylinux2010', 'x86', 'cp37-cp37m'),
@@ -380,19 +376,16 @@ def targets():
         PythonArtifact('linux_extra', 'armv7', 'cp37-cp37m'),
         PythonArtifact('linux_extra', 'armv7', 'cp38-cp38'),
         PythonArtifact('linux_extra', 'armv7', 'cp39-cp39'),
-        PythonArtifact('macos', 'x64', 'python2.7'),
         PythonArtifact('macos', 'x64', 'python3.5'),
         PythonArtifact('macos', 'x64', 'python3.6'),
         PythonArtifact('macos', 'x64', 'python3.7'),
         PythonArtifact('macos', 'x64', 'python3.8'),
         PythonArtifact('macos', 'x64', 'python3.9'),
-        PythonArtifact('windows', 'x86', 'Python27_32bit'),
         PythonArtifact('windows', 'x86', 'Python35_32bit'),
         PythonArtifact('windows', 'x86', 'Python36_32bit'),
         PythonArtifact('windows', 'x86', 'Python37_32bit'),
         PythonArtifact('windows', 'x86', 'Python38_32bit'),
         PythonArtifact('windows', 'x86', 'Python39_32bit'),
-        PythonArtifact('windows', 'x64', 'Python27'),
         PythonArtifact('windows', 'x64', 'Python35'),
         PythonArtifact('windows', 'x64', 'Python36'),
         PythonArtifact('windows', 'x64', 'Python37'),
diff --git a/tools/run_tests/artifacts/distribtest_targets.py b/tools/run_tests/artifacts/distribtest_targets.py
index a2c8d6b1cdd..23798331553 100644
--- a/tools/run_tests/artifacts/distribtest_targets.py
+++ b/tools/run_tests/artifacts/distribtest_targets.py
@@ -344,11 +344,10 @@ def targets():
         CSharpDistribTest('windows', 'x86'),
         CSharpDistribTest('windows', 'x64'),
         # Python
-        PythonDistribTest('linux', 'x64', 'jessie'),
-        PythonDistribTest('linux', 'x86', 'jessie'),
-        PythonDistribTest('linux', 'x64', 'centos6'),
+        PythonDistribTest('linux', 'x64', 'stretch'),
+        PythonDistribTest('linux', 'x86', 'stretch'),
         PythonDistribTest('linux', 'x64', 'centos7'),
-        PythonDistribTest('linux', 'x64', 'fedora23'),
+        PythonDistribTest('linux', 'x64', 'fedora34'),
         PythonDistribTest('linux', 'x64', 'opensuse'),
         PythonDistribTest('linux', 'x64', 'arch'),
         PythonDistribTest('linux', 'x64', 'ubuntu1604'),
diff --git a/tools/run_tests/run_tests.py b/tools/run_tests/run_tests.py
index 7940e5ad23d..75c99f7fabb 100755
--- a/tools/run_tests/run_tests.py
+++ b/tools/run_tests/run_tests.py
@@ -775,6 +775,11 @@ class PythonLanguage(object):
                                                    minor='8',
                                                    bits=bits,
                                                    config_vars=config_vars)
+        python39_config = _python_config_generator(name='py39',
+                                                   major='3',
+                                                   minor='9',
+                                                   bits=bits,
+                                                   config_vars=config_vars)
         pypy27_config = _pypy_config_generator(name='pypy',
                                                major='2',
                                                config_vars=config_vars)
@@ -804,13 +809,9 @@ class PythonLanguage(object):
                     # NOTE(rbellevi): Testing takes significantly longer on
                     # MacOS, so we restrict the number of interpreter versions
                     # tested.
-                    return (
-                        python27_config,
-                        python38_config,
-                    )
+                    return (python38_config,)
                 else:
                     return (
-                        python27_config,
                         python35_config,
                         python37_config,
                         python38_config,
@@ -825,6 +826,8 @@ class PythonLanguage(object):
             return (python37_config,)
         elif args.compiler == 'python3.8':
             return (python38_config,)
+        elif args.compiler == 'python3.9':
+            return (python39_config,)
         elif args.compiler == 'pypy':
             return (pypy27_config,)
         elif args.compiler == 'pypy3':