diff --git a/compiler-rt/test/asan/lit.cfg.py b/compiler-rt/test/asan/lit.cfg.py
--- a/compiler-rt/test/asan/lit.cfg.py
+++ b/compiler-rt/test/asan/lit.cfg.py
@@ -247,3 +247,10 @@
 
 if config.host_os == 'NetBSD':
   config.substitutions.insert(0, ('%run', config.netbsd_noaslr_prefix))
+
+# 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"
diff --git a/compiler-rt/test/cfi/lit.cfg.py b/compiler-rt/test/cfi/lit.cfg.py
--- a/compiler-rt/test/cfi/lit.cfg.py
+++ b/compiler-rt/test/cfi/lit.cfg.py
@@ -48,3 +48,10 @@
 
 if lit_config.params.get('check_supported', None) and config.unsupported:
   raise BaseException("Tests unsupported")
+
+# 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"
diff --git a/compiler-rt/test/dfsan/lit.cfg.py b/compiler-rt/test/dfsan/lit.cfg.py
--- a/compiler-rt/test/dfsan/lit.cfg.py
+++ b/compiler-rt/test/dfsan/lit.cfg.py
@@ -26,3 +26,10 @@
 # DataFlowSanitizer tests are currently supported on Linux only.
 if not (config.host_os in ['Linux'] and config.target_arch in ['aarch64', 'x86_64']):
   config.unsupported = True
+
+# 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"
diff --git a/compiler-rt/test/fuzzer/lit.cfg.py b/compiler-rt/test/fuzzer/lit.cfg.py
--- a/compiler-rt/test/fuzzer/lit.cfg.py
+++ b/compiler-rt/test/fuzzer/lit.cfg.py
@@ -124,3 +124,10 @@
 
 if config.host_os == 'NetBSD':
   config.substitutions.insert(0, ('%run', config.netbsd_noaslr_prefix))
+
+# 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"
diff --git a/compiler-rt/test/gwp_asan/lit.cfg.py b/compiler-rt/test/gwp_asan/lit.cfg.py
--- a/compiler-rt/test/gwp_asan/lit.cfg.py
+++ b/compiler-rt/test/gwp_asan/lit.cfg.py
@@ -54,3 +54,10 @@
 # GWP-ASan tests are currently supported on Linux only.
 if config.host_os not in ['Linux']:
    config.unsupported = True
+
+# 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"
diff --git a/compiler-rt/test/hwasan/lit.cfg.py b/compiler-rt/test/hwasan/lit.cfg.py
--- a/compiler-rt/test/hwasan/lit.cfg.py
+++ b/compiler-rt/test/hwasan/lit.cfg.py
@@ -56,3 +56,10 @@
 
 if config.host_os not in ['Linux', 'Android'] or not config.has_lld:
   config.unsupported = True
+
+# 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"
diff --git a/compiler-rt/test/msan/lit.cfg.py b/compiler-rt/test/msan/lit.cfg.py
--- a/compiler-rt/test/msan/lit.cfg.py
+++ b/compiler-rt/test/msan/lit.cfg.py
@@ -51,3 +51,10 @@
 
 if config.host_os == 'NetBSD':
   config.substitutions.insert(0, ('%run', config.netbsd_noaslr_prefix))
+
+# 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"
diff --git a/compiler-rt/test/safestack/lit.cfg.py b/compiler-rt/test/safestack/lit.cfg.py
--- a/compiler-rt/test/safestack/lit.cfg.py
+++ b/compiler-rt/test/safestack/lit.cfg.py
@@ -20,3 +20,10 @@
 
 if config.host_os not in ['Linux', 'FreeBSD', 'NetBSD']:
    config.unsupported = True
+
+# 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"
diff --git a/compiler-rt/test/scudo/lit.cfg.py b/compiler-rt/test/scudo/lit.cfg.py
--- a/compiler-rt/test/scudo/lit.cfg.py
+++ b/compiler-rt/test/scudo/lit.cfg.py
@@ -62,3 +62,10 @@
 # Hardened Allocator tests are currently supported on Linux only.
 if config.host_os not in ['Linux']:
    config.unsupported = True
+
+# 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"
diff --git a/compiler-rt/test/shadowcallstack/lit.cfg.py b/compiler-rt/test/shadowcallstack/lit.cfg.py
--- a/compiler-rt/test/shadowcallstack/lit.cfg.py
+++ b/compiler-rt/test/shadowcallstack/lit.cfg.py
@@ -21,3 +21,10 @@
 
 if config.host_os not in ['Linux'] or config.target_arch not in ['aarch64']:
    config.unsupported = True
+
+# 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"
diff --git a/compiler-rt/test/tsan/lit.cfg.py b/compiler-rt/test/tsan/lit.cfg.py
--- a/compiler-rt/test/tsan/lit.cfg.py
+++ b/compiler-rt/test/tsan/lit.cfg.py
@@ -92,3 +92,10 @@
 
 if config.host_os == 'NetBSD':
   config.substitutions.insert(0, ('%run', config.netbsd_noaslr_prefix))
+
+# 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"
diff --git a/compiler-rt/test/xray/lit.cfg.py b/compiler-rt/test/xray/lit.cfg.py
--- a/compiler-rt/test/xray/lit.cfg.py
+++ b/compiler-rt/test/xray/lit.cfg.py
@@ -64,3 +64,10 @@
 
 if config.host_os == 'NetBSD':
   config.substitutions.insert(0, ('%run', config.netbsd_nomprotect_prefix))
+
+# 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"