diff --git a/compiler-rt/test/lit.common.cfg.py b/compiler-rt/test/lit.common.cfg.py
--- a/compiler-rt/test/lit.common.cfg.py
+++ b/compiler-rt/test/lit.common.cfg.py
@@ -733,3 +733,10 @@
       sh_quote(get_ios_commands_dir())
     ))
   )
+
+# It is not realistically possible to account for all options that could
+# possibly be present in system and user configuration files, so disable
+# default configs for the test runs. In particular, anything hardening
+# related is likely to cause issues with sanitizer tests, because it may
+# preempt something we're looking to trap (e.g. FORTIFY_SOURCE vs our ASAN).
+config.environment["CLANG_NO_DEFAULT_CONFIG"] = "1"