diff --git a/flang-rt/test/Driver/ctofortran.f90 b/flang-rt/test/Driver/ctofortran.f90
index e385e7974cdc1..4979a4e68da59 100644
--- a/flang-rt/test/Driver/ctofortran.f90
+++ b/flang-rt/test/Driver/ctofortran.f90
@@ -2,8 +2,8 @@
 ! UNSUPPORTED: offload-cuda
 
 ! RUN: split-file %s %t
-! RUN: %clang -I"%include/flang" -c %t/cfile.c -o %t/cfile.o
-! RUN: %flang -L"%libdir" %t/ffile.f90 %t/cfile.o -o %t/ctofortran
+! RUN: %clang %isysroot -I"%include/flang" -c %t/cfile.c -o %t/cfile.o
+! RUN: %flang %isysroot -L"%libdir" %t/ffile.f90 %t/cfile.o -o %t/ctofortran
 ! RUN: env LD_LIBRARY_PATH="$LD_LIBRARY_PATH:%libdir" %t/ctofortran | FileCheck %s
 
 !--- ffile.f90
diff --git a/flang-rt/test/Runtime/no-cpp-dep.c b/flang-rt/test/Runtime/no-cpp-dep.c
index c98678b69aa14..006f44b4aff7a 100644
--- a/flang-rt/test/Runtime/no-cpp-dep.c
+++ b/flang-rt/test/Runtime/no-cpp-dep.c
@@ -7,7 +7,7 @@ UNSUPPORTED: system-windows
 UNSUPPORTED: offload-cuda
 
 RUN: %if system-aix %{ export OBJECT_MODE=64 %}
-RUN: %cc -std=c99 %s -I%include -L"%libdir" -lflang_rt.runtime -lm \
+RUN: %cc -std=c99 %s %isysroot -I%include -L"%libdir" -lflang_rt.runtime -lm \
 RUN: %if system-aix %{-lpthread %}
 RUN: rm a.out
 */
diff --git a/flang-rt/test/lit.cfg.py b/flang-rt/test/lit.cfg.py
index 032aeef2d5bf6..27f4666a4a42a 100644
--- a/flang-rt/test/lit.cfg.py
+++ b/flang-rt/test/lit.cfg.py
@@ -62,25 +62,24 @@ def shjoin(args, sep=" "):
 # lit writes a '.lit_test_times.txt' file into this directory.
 config.test_exec_root = config.flang_rt_binary_test_dir
 
-# On MacOS, -isysroot is needed to build binaries.
+# On MacOS, some tests need -isysroot to build binaries.
 isysroot_flag = []
 if config.osx_sysroot:
     isysroot_flag = ["-isysroot", config.osx_sysroot]
+config.substitutions.append(("%isysroot", " ".join(isysroot_flag)))
 
 tools = [
     ToolSubst(
         "%flang",
         command=config.flang,
-        extra_args=isysroot_flag,
         unresolved="fatal",
     ),
     ToolSubst(
         "%clang",
         command=FindTool("clang"),
-        extra_args=isysroot_flag,
         unresolved="fatal",
     ),
-    ToolSubst("%cc", command=config.cc, extra_args=isysroot_flag, unresolved="fatal"),
+    ToolSubst("%cc", command=config.cc, unresolved="fatal"),
 ]
 llvm_config.add_tool_substitutions(tools)
 
diff --git a/flang/CMakeLists.txt b/flang/CMakeLists.txt
index 1d16c33f44900..c01eb56d5e496 100644
--- a/flang/CMakeLists.txt
+++ b/flang/CMakeLists.txt
@@ -495,6 +495,9 @@ endif()
 
 include(AddFlang)
 include(FlangCommon)
+include(GetClangResourceDir)
+
+get_clang_resource_dir(HEADER_BINARY_DIR PREFIX ${LLVM_LIBRARY_OUTPUT_INTDIR}/.. SUBDIR include)
 
 if (FLANG_INCLUDE_TESTS)
   add_compile_definitions(FLANG_INCLUDE_TESTS=1)
@@ -575,8 +578,6 @@ endif()
 
 # Put ISO_Fortran_binding.h into the include files of the build area now
 # so that we can run tests before installing
-include(GetClangResourceDir)
-get_clang_resource_dir(HEADER_BINARY_DIR PREFIX ${LLVM_LIBRARY_OUTPUT_INTDIR}/.. SUBDIR include)
 configure_file(
   ${FLANG_SOURCE_DIR}/include/flang/ISO_Fortran_binding.h
   ${HEADER_BINARY_DIR}/ISO_Fortran_binding.h COPYONLY)
diff --git a/flang/test/Integration/iso-fortran-binding.cpp b/flang/test/Integration/iso-fortran-binding.cpp
index aaafd7cccd07d..36ae35d9d29f7 100644
--- a/flang/test/Integration/iso-fortran-binding.cpp
+++ b/flang/test/Integration/iso-fortran-binding.cpp
@@ -1,9 +1,9 @@
+// REQUIRES: clang
 // UNSUPPORTED: system-windows
-// RUN: split-file %s %t
-// RUN: chmod +x %t/runtest.sh
-// RUN: %t/runtest.sh %t %t/cppfile.cpp %flang | FileCheck %s
+// RUN: rm -rf %t && mkdir %t
+// RUN: %clangxx %isysroot -I%flang_include %s -o %t/a.out
+// RUN: %t/a.out | FileCheck %s
 
-//--- cppfile.cpp
 extern "C" {
 #include "ISO_Fortran_binding.h"
 }
@@ -15,19 +15,3 @@ int main() {
 }
 
 // CHECK: PASS
-// clang-format off
-//--- runtest.sh
-#!/bin/bash
-TMPDIR=$1
-CPPFILE=$2
-FLANG=$3
-BINDIR=`dirname $FLANG`
-CPPCOMP=$BINDIR/clang++
-if [ -x $CPPCOMP ]
-then
-  $CPPCOMP $CPPFILE -o $TMPDIR/a.out
-  $TMPDIR/a.out # should print "PASS"
-else
-  # No clang compiler, just pass by default
-  echo "PASS"
-fi
diff --git a/flang/test/lit.cfg.py b/flang/test/lit.cfg.py
index 7eb57670ac767..9d81aa41384ed 100644
--- a/flang/test/lit.cfg.py
+++ b/flang/test/lit.cfg.py
@@ -118,10 +118,11 @@
                 "PATH", config.flang_llvm_tools_dir, append_path=True
             )
 
-# On MacOS, -isysroot is needed to build binaries.
+# On MacOS, some tests need -isysroot to build binaries.
 isysroot_flag = []
 if config.osx_sysroot:
     isysroot_flag = ["-isysroot", config.osx_sysroot]
+config.substitutions.append(("%isysroot", " ".join(isysroot_flag)))
 
 # Check for DEFAULT_SYSROOT, because when it is set -isysroot has no effect.
 if config.default_sysroot:
@@ -133,7 +134,6 @@
     ToolSubst(
         "%flang",
         command=FindTool("flang"),
-        extra_args=isysroot_flag,
         unresolved="fatal",
     ),
     ToolSubst(
@@ -172,6 +172,11 @@
 else:
     llvm_config.add_tool_substitutions(tools, config.llvm_tools_dir)
 
+llvm_config.use_clang(required=False)
+
+# Clang may need the include path for ISO_fortran_binding.h.
+config.substitutions.append(("%flang_include", config.flang_headers_dir))
+
 # Enable libpgmath testing
 result = lit_config.params.get("LIBPGMATH")
 if result:
diff --git a/flang/test/lit.site.cfg.py.in b/flang/test/lit.site.cfg.py.in
index ae5144010bc8b..cc1f4fa6cc9c5 100644
--- a/flang/test/lit.site.cfg.py.in
+++ b/flang/test/lit.site.cfg.py.in
@@ -6,6 +6,7 @@ import lit.util
 config.llvm_tools_dir = lit_config.substitute("@LLVM_TOOLS_DIR@")
 config.llvm_shlib_dir = lit_config.substitute(path(r"@SHLIBDIR@"))
 config.llvm_plugin_ext = "@LLVM_PLUGIN_EXT@"
+config.host_triple = "@LLVM_HOST_TRIPLE@"
 config.target_triple = "@LLVM_TARGET_TRIPLE@"
 config.llvm_target_triple_env = "@LLVM_TARGET_TRIPLE_ENV@"
 config.lit_tools_dir = "@LLVM_LIT_TOOLS_DIR@"
@@ -13,6 +14,7 @@ config.errc_messages = "@LLVM_LIT_ERRC_MESSAGES@"
 config.flang_obj_root = "@FLANG_BINARY_DIR@"
 config.flang_tools_dir = lit_config.substitute("@FLANG_TOOLS_DIR@")
 config.flang_intrinsic_modules_dir = "@FLANG_INTRINSIC_MODULES_DIR@"
+config.flang_headers_dir = "@HEADER_BINARY_DIR@"
 config.flang_llvm_tools_dir = "@CMAKE_BINARY_DIR@/bin"
 config.flang_test_triple = "@FLANG_TEST_TARGET_TRIPLE@"
 config.flang_examples = @LLVM_BUILD_EXAMPLES@