diff --git a/CHANGES.txt b/CHANGES.txt
index 88e940c280..672711f697 100644
--- a/CHANGES.txt
+++ b/CHANGES.txt
@@ -1,4 +1,5 @@
 5.1
+ * Provide clearer exception message on failing commitlog_disk_access_mode combinations (CASSANDRA-19812)
  * Add total space used for a keyspace to nodetool tablestats (CASSANDRA-19671)
  * Ensure Relation#toRestriction() handles ReversedType properly (CASSANDRA-19950)
  * Add JSON and YAML output option to nodetool gcstats (CASSANDRA-19771)
diff --git a/src/java/org/apache/cassandra/config/DatabaseDescriptor.java b/src/java/org/apache/cassandra/config/DatabaseDescriptor.java
index 66e0fd0532..7009da0aba 100644
--- a/src/java/org/apache/cassandra/config/DatabaseDescriptor.java
+++ b/src/java/org/apache/cassandra/config/DatabaseDescriptor.java
@@ -1562,7 +1562,14 @@ public class DatabaseDescriptor
         }
         else if (compressOrEncrypt && accessModeDirectIoPair.left != DiskAccessMode.standard)
         {
-            throw new ConfigurationException("commitlog_disk_access_mode = " + accessModeDirectIoPair.left + " is not supported with compression or encryption. Please use 'auto' when unsure.", false);
+            String with;
+            if (null != getCommitLogCompression() && (null != getEncryptionContext() && getEncryptionContext().isEnabled()))
+                with = "compression or encryption";
+            else if (null != getCommitLogCompression())
+                with = "compression";
+            else
+                with = "encryption";
+            throw new ConfigurationException("commitlog_disk_access_mode = " + accessModeDirectIoPair.left + " is not supported with " + with + ". Please use 'auto' when unsure.", false);
         }
         else if (!compressOrEncrypt && accessModeDirectIoPair.left != DiskAccessMode.mmap && accessModeDirectIoPair.left != DiskAccessMode.direct)
         {
diff --git a/test/unit/org/apache/cassandra/cql3/CQLTester.java b/test/unit/org/apache/cassandra/cql3/CQLTester.java
index 6d67c05ced..624b069e9c 100644
--- a/test/unit/org/apache/cassandra/cql3/CQLTester.java
+++ b/test/unit/org/apache/cassandra/cql3/CQLTester.java
@@ -3070,10 +3070,10 @@ public abstract class CQLTester
             Map<String, Object> config = CONFIG_GEN.next(RANDOM);
             CONFIG = YamlConfigurationLoader.toYaml(config);
 
-            Config c = ConfigGenBuilder.sanitize(DatabaseDescriptor.loadConfig());
+            Config c = ConfigGenBuilder.prepare(DatabaseDescriptor.loadConfig());
             YamlConfigurationLoader.updateFromMap(config, true, c);
 
-            DatabaseDescriptor.unsafeDaemonInitialization(() -> c);
+            DatabaseDescriptor.unsafeDaemonInitialization(() -> ConfigGenBuilder.sanitize(c));
         }
 
         public static class FailureWatcher extends TestWatcher
diff --git a/test/unit/org/apache/cassandra/utils/ConfigGenBuilder.java b/test/unit/org/apache/cassandra/utils/ConfigGenBuilder.java
index f339e42522..c103a8dc6d 100644
--- a/test/unit/org/apache/cassandra/utils/ConfigGenBuilder.java
+++ b/test/unit/org/apache/cassandra/utils/ConfigGenBuilder.java
@@ -37,12 +37,23 @@ public class ConfigGenBuilder
     public enum Memtable
     {SkipListMemtable, TrieMemtable, ShardedSkipListMemtable}
 
+    private static boolean validCommitLogDiskAccessMode(Config c)
+    {
+        Config.DiskAccessMode m = c.commitlog_disk_access_mode;
+
+        return null != c.commitlog_compression
+            ? Config.DiskAccessMode.standard == m
+            : Config.DiskAccessMode.mmap == m || Config.DiskAccessMode.direct == m;
+    }
+
     @Nullable
     Gen<IPartitioner> partitionerGen = Generators.toGen(CassandraGenerators.nonLocalPartitioners());
+
     Gen<Config.DiskAccessMode> commitLogDiskAccessModeGen = Gens.enums().all(Config.DiskAccessMode.class)
                                                                 .filter(m -> m != Config.DiskAccessMode.standard
                                                                              && m != Config.DiskAccessMode.mmap_index_only
                                                                              && m != Config.DiskAccessMode.direct); // don't allow direct as not every filesystem supports it, making the config environment specific
+
     Gen<Config.DiskAccessMode> diskAccessModeGen = Gens.enums().all(Config.DiskAccessMode.class).filter(m -> m != Config.DiskAccessMode.direct);
     Gen<String> sstableFormatGen = Generators.toGen(CassandraGenerators.sstableFormatNames());
     Gen<Config.MemtableAllocationType> memtableAllocationTypeGen = Gens.enums().all(Config.MemtableAllocationType.class);
@@ -71,7 +82,7 @@ public class ConfigGenBuilder
     /**
      * When loading the {@link Config} from a yaml its possible that some configs set will conflict with the configs that get generated here, to avoid that set them to a good default
      */
-    public static Config sanitize(Config config)
+    public static Config prepare(Config config)
     {
         Config defaults = new Config();
         config.commitlog_sync = defaults.commitlog_sync;
@@ -80,6 +91,18 @@ public class ConfigGenBuilder
         return config;
     }
 
+    /**
+     * After loading from yaml, sanitize the resulting config to avoid fast-failures on illegal combinations
+     */
+    public static Config sanitize(Config config)
+    {
+        // if commitlog_disk_access_mode has been generated to something other than standard, make sure compression is disabled
+        if (null != config.commitlog_compression && Config.DiskAccessMode.standard != config.commitlog_disk_access_mode)
+            config.commitlog_compression = null;
+
+        return config;
+    }
+
     public ConfigGenBuilder withPartitioner(IPartitioner instance)
     {
         this.partitionerGen = ignore -> instance;
diff --git a/test/unit/org/apache/cassandra/utils/ConfigGenBuilderTest.java b/test/unit/org/apache/cassandra/utils/ConfigGenBuilderTest.java
index 0c2aaf29ad..6bae12c319 100644
--- a/test/unit/org/apache/cassandra/utils/ConfigGenBuilderTest.java
+++ b/test/unit/org/apache/cassandra/utils/ConfigGenBuilderTest.java
@@ -57,12 +57,12 @@ public class ConfigGenBuilderTest
     private static void validate(Map<String, Object> config, Config c)
     {
         YamlConfigurationLoader.updateFromMap(config, true, c);
-        DatabaseDescriptor.unsafeDaemonInitialization(() -> c);
+        DatabaseDescriptor.unsafeDaemonInitialization(() -> ConfigGenBuilder.sanitize(c));
     }
 
     private static Config defaultConfig()
     {
-        return ConfigGenBuilder.sanitize(DatabaseDescriptor.loadConfig());
+        return ConfigGenBuilder.prepare(DatabaseDescriptor.loadConfig());
     }
 
     private static Config simpleConfig()