diff --git a/libcxx/CMakeLists.txt b/libcxx/CMakeLists.txt
index 85514cc7547a9..b4c901fb142ca 100644
--- a/libcxx/CMakeLists.txt
+++ b/libcxx/CMakeLists.txt
@@ -751,6 +751,18 @@ config_define(${LIBCXX_ENABLE_WIDE_CHARACTERS} _LIBCPP_HAS_WIDE_CHARACTERS)
 config_define(${LIBCXX_ENABLE_TIME_ZONE_DATABASE} _LIBCPP_HAS_TIME_ZONE_DATABASE)
 config_define(${LIBCXX_ENABLE_VENDOR_AVAILABILITY_ANNOTATIONS} _LIBCPP_HAS_VENDOR_AVAILABILITY_ANNOTATIONS)
 
+# Set C library in use
+if (RUNTIMES_USE_LIBC STREQUAL "picolibc")
+  config_define(1 _LIBCXX_LIBC_PICOLIBC)
+  # picolibc is derived from newlib and behaves the same in regards to libc++
+  # so setting both here:
+  # * _LIBCXX_LIBC_NEWLIB is used now
+  # * _LIBCXX_LIBC_PICOLIBC can be used for further customizations later
+  config_define(1 _LIBCXX_LIBC_NEWLIB)
+elseif (RUNTIMES_USE_LIBC STREQUAL "newlib")
+  config_define(1 _LIBCXX_LIBC_NEWLIB)
+endif()
+
 # TODO: Remove in LLVM 21. We're leaving an error to make this fail explicitly.
 if (LIBCXX_ENABLE_ASSERTIONS)
   message(FATAL_ERROR "LIBCXX_ENABLE_ASSERTIONS has been removed. Please use LIBCXX_HARDENING_MODE instead.")
diff --git a/libcxx/include/__config_site.in b/libcxx/include/__config_site.in
index fc01aaf2d8746..a4f32570385e1 100644
--- a/libcxx/include/__config_site.in
+++ b/libcxx/include/__config_site.in
@@ -42,6 +42,10 @@
 // Hardening.
 #cmakedefine _LIBCPP_HARDENING_MODE_DEFAULT @_LIBCPP_HARDENING_MODE_DEFAULT@
 
+// C libraries
+#cmakedefine01 _LIBCXX_LIBC_PICOLIBC
+#cmakedefine01 _LIBCXX_LIBC_NEWLIB
+
 // __USE_MINGW_ANSI_STDIO gets redefined on MinGW
 #ifdef __clang__
 #  pragma clang diagnostic push
diff --git a/libcxx/include/__configuration/platform.h b/libcxx/include/__configuration/platform.h
index f3c199dee172b..8d0f8f63f5213 100644
--- a/libcxx/include/__configuration/platform.h
+++ b/libcxx/include/__configuration/platform.h
@@ -42,13 +42,6 @@
 #  endif
 #endif
 
-// This is required in order for _NEWLIB_VERSION to be defined in places where we use it.
-// TODO: We shouldn't be including arbitrarily-named headers from libc++ since this can break valid
-//       user code. Move code paths that need _NEWLIB_VERSION to another customization mechanism.
-#if __has_include(<picolibc.h>)
-#  include <picolibc.h>
-#endif
-
 #ifndef __BYTE_ORDER__
 #  error                                                                                                               \
       "Your compiler doesn't seem to define __BYTE_ORDER__, which is required by libc++ to know the endianness of your target platform"
diff --git a/libcxx/include/__cxx03/__fwd/ios.h b/libcxx/include/__cxx03/__fwd/ios.h
index dc03e8c6bab2f..62c267d03301d 100644
--- a/libcxx/include/__cxx03/__fwd/ios.h
+++ b/libcxx/include/__cxx03/__fwd/ios.h
@@ -31,7 +31,7 @@ using wios = basic_ios<wchar_t>;
 template <class _CharT, class _Traits>
 class _LIBCPP_PREFERRED_NAME(ios) _LIBCPP_IF_WIDE_CHARACTERS(_LIBCPP_PREFERRED_NAME(wios)) basic_ios;
 
-#if defined(_NEWLIB_VERSION)
+#if _LIBCXX_LIBC_NEWLIB
 // On newlib, off_t is 'long int'
 using streamoff = long int; // for char_traits in <string>
 #else
diff --git a/libcxx/include/__cxx03/__locale b/libcxx/include/__cxx03/__locale
index d5faa89b99fc0..a2d971f056d18 100644
--- a/libcxx/include/__cxx03/__locale
+++ b/libcxx/include/__cxx03/__locale
@@ -384,7 +384,7 @@ public:
   static const mask xdigit       = _ISXDIGIT;
   static const mask blank        = _ISBLANK;
   static const mask __regex_word = 0x8000;
-#elif defined(_NEWLIB_VERSION)
+#elif _LIBCXX_LIBC_NEWLIB
   // Same type as Newlib's _ctype_ array in newlib/libc/include/ctype.h.
   typedef char mask;
   // In case char is signed, static_cast is needed to avoid warning on
diff --git a/libcxx/include/__cxx03/__locale_dir/locale_base_api.h b/libcxx/include/__cxx03/__locale_dir/locale_base_api.h
index a20f0952f52c3..e10db1dfa378f 100644
--- a/libcxx/include/__cxx03/__locale_dir/locale_base_api.h
+++ b/libcxx/include/__cxx03/__locale_dir/locale_base_api.h
@@ -17,7 +17,7 @@
 #  include <__cxx03/__locale_dir/locale_base_api/android.h>
 #elif defined(__sun__)
 #  include <__cxx03/__locale_dir/locale_base_api/solaris.h>
-#elif defined(_NEWLIB_VERSION)
+#elif _LIBCXX_LIBC_NEWLIB
 #  include <__cxx03/__locale_dir/locale_base_api/newlib.h>
 #elif defined(__OpenBSD__)
 #  include <__cxx03/__locale_dir/locale_base_api/openbsd.h>
diff --git a/libcxx/include/__cxx03/fstream b/libcxx/include/__cxx03/fstream
index 44bdabc4602b5..db7b87343fef1 100644
--- a/libcxx/include/__cxx03/fstream
+++ b/libcxx/include/__cxx03/fstream
@@ -209,7 +209,7 @@ typedef basic_fstream<wchar_t> wfstream;
 _LIBCPP_PUSH_MACROS
 #include <__cxx03/__undef_macros>
 
-#if defined(_LIBCPP_MSVCRT) || defined(_NEWLIB_VERSION)
+#if defined(_LIBCPP_MSVCRT) || _LIBCXX_LIBC_NEWLIB
 #  define _LIBCPP_HAS_NO_OFF_T_FUNCTIONS
 #endif
 
diff --git a/libcxx/include/__cxx03/locale b/libcxx/include/__cxx03/locale
index 64162f5a4ff2c..771a3441e10d9 100644
--- a/libcxx/include/__cxx03/locale
+++ b/libcxx/include/__cxx03/locale
@@ -220,7 +220,7 @@ template <class charT> class messages_byname;
 
 #  if defined(__unix__) || (defined(__APPLE__) && defined(__MACH__))
 // Most unix variants have catopen.  These are the specific ones that don't.
-#    if !defined(__BIONIC__) && !defined(_NEWLIB_VERSION) && !defined(__EMSCRIPTEN__)
+#    if !defined(__BIONIC__) && !_LIBCXX_LIBC_NEWLIB && !defined(__EMSCRIPTEN__)
 #      define _LIBCPP_HAS_CATOPEN 1
 #      include <nl_types.h>
 #    endif
diff --git a/libcxx/include/__cxx03/regex b/libcxx/include/__cxx03/regex
index b96d59d3a252a..0efc56c8a95d0 100644
--- a/libcxx/include/__cxx03/regex
+++ b/libcxx/include/__cxx03/regex
@@ -984,7 +984,7 @@ public:
   typedef _CharT char_type;
   typedef basic_string<char_type> string_type;
   typedef locale locale_type;
-#if defined(__BIONIC__) || defined(_NEWLIB_VERSION)
+#if defined(__BIONIC__) || _LIBCXX_LIBC_NEWLIB
   // Originally bionic's ctype_base used its own ctype masks because the
   // builtin ctype implementation wasn't in libc++ yet. Bionic's ctype mask
   // was only 8 bits wide and already saturated, so it used a wider type here
@@ -993,9 +993,7 @@ public:
   // implementation, but this was not updated to match. Since then Android has
   // needed to maintain a stable libc++ ABI, and this can't be changed without
   // an ABI break.
-  // We also need this workaround for newlib since _NEWLIB_VERSION is not
-  // defined yet inside __config, so we can't set the
-  // _LIBCPP_PROVIDES_DEFAULT_RUNE_TABLE macro. Additionally, newlib is
+  // We also need this workaround for newlib since newlib is
   // often used for space constrained environments, so it makes sense not to
   // duplicate the ctype table.
   typedef uint16_t char_class_type;
diff --git a/libcxx/include/__fwd/ios.h b/libcxx/include/__fwd/ios.h
index 831624f4b1c57..92c58250020dd 100644
--- a/libcxx/include/__fwd/ios.h
+++ b/libcxx/include/__fwd/ios.h
@@ -31,7 +31,7 @@ using wios = basic_ios<wchar_t>;
 template <class _CharT, class _Traits>
 class _LIBCPP_PREFERRED_NAME(ios) _LIBCPP_IF_WIDE_CHARACTERS(_LIBCPP_PREFERRED_NAME(wios)) basic_ios;
 
-#if defined(_NEWLIB_VERSION)
+#if _LIBCXX_LIBC_NEWLIB
 // On newlib, off_t is 'long int'
 using streamoff = long int; // for char_traits in <string>
 #else
diff --git a/libcxx/include/__locale b/libcxx/include/__locale
index 757a53951f66e..da3c0501cc22c 100644
--- a/libcxx/include/__locale
+++ b/libcxx/include/__locale
@@ -389,7 +389,7 @@ public:
   static const mask xdigit       = _ISXDIGIT;
   static const mask blank        = _ISBLANK;
   static const mask __regex_word = 0x8000;
-#  elif defined(_NEWLIB_VERSION)
+#  elif _LIBCXX_LIBC_NEWLIB
   // Same type as Newlib's _ctype_ array in newlib/libc/include/ctype.h.
   typedef char mask;
   // In case char is signed, static_cast is needed to avoid warning on
diff --git a/libcxx/include/__locale_dir/messages.h b/libcxx/include/__locale_dir/messages.h
index c04bf04025ff0..dba8be512821d 100644
--- a/libcxx/include/__locale_dir/messages.h
+++ b/libcxx/include/__locale_dir/messages.h
@@ -22,7 +22,7 @@
 
 #  if defined(__unix__) || (defined(__APPLE__) && defined(__MACH__))
 // Most unix variants have catopen.  These are the specific ones that don't.
-#    if !defined(__BIONIC__) && !defined(_NEWLIB_VERSION) && !defined(__EMSCRIPTEN__)
+#    if !defined(__BIONIC__) && !_LIBCXX_LIBC_NEWLIB && !defined(__EMSCRIPTEN__)
 #      define _LIBCPP_HAS_CATOPEN 1
 #      include <nl_types.h>
 #    else
diff --git a/libcxx/include/fstream b/libcxx/include/fstream
index c86f709bedb80..47534bfef34f4 100644
--- a/libcxx/include/fstream
+++ b/libcxx/include/fstream
@@ -964,7 +964,7 @@ template <class _CharT, class _Traits>
 int basic_filebuf<_CharT, _Traits>::__fseek(FILE* __file, pos_type __offset, int __whence) {
 #    if defined(_LIBCPP_MSVCRT_LIKE)
   return _fseeki64(__file, __offset, __whence);
-#    elif defined(_NEWLIB_VERSION)
+#    elif _LIBCXX_LIBC_NEWLIB
   return fseek(__file, __offset, __whence);
 #    else
   return ::fseeko(__file, __offset, __whence);
@@ -975,7 +975,7 @@ template <class _CharT, class _Traits>
 typename basic_filebuf<_CharT, _Traits>::pos_type basic_filebuf<_CharT, _Traits>::__ftell(FILE* __file) {
 #    if defined(_LIBCPP_MSVCRT_LIKE)
   return _ftelli64(__file);
-#    elif defined(_NEWLIB_VERSION)
+#    elif _LIBCXX_LIBC_NEWLIB
   return ftell(__file);
 #    else
   return ftello(__file);
diff --git a/libcxx/include/regex b/libcxx/include/regex
index bbc21e244dd17..5f84c44f8c448 100644
--- a/libcxx/include/regex
+++ b/libcxx/include/regex
@@ -1004,7 +1004,7 @@ public:
   typedef _CharT char_type;
   typedef basic_string<char_type> string_type;
   typedef locale locale_type;
-#    if defined(__BIONIC__) || defined(_NEWLIB_VERSION)
+#    if defined(__BIONIC__) || _LIBCXX_LIBC_NEWLIB
   // Originally bionic's ctype_base used its own ctype masks because the
   // builtin ctype implementation wasn't in libc++ yet. Bionic's ctype mask
   // was only 8 bits wide and already saturated, so it used a wider type here
@@ -1013,9 +1013,7 @@ public:
   // implementation, but this was not updated to match. Since then Android has
   // needed to maintain a stable libc++ ABI, and this can't be changed without
   // an ABI break.
-  // We also need this workaround for newlib since _NEWLIB_VERSION is not
-  // defined yet inside __config, so we can't set the
-  // _LIBCPP_PROVIDES_DEFAULT_RUNE_TABLE macro. Additionally, newlib is
+  // We also need this workaround for newlib since newlib is
   // often used for space constrained environments, so it makes sense not to
   // duplicate the ctype table.
   typedef uint16_t char_class_type;
diff --git a/libcxx/src/include/config_elast.h b/libcxx/src/include/config_elast.h
index 7edff2d9375d4..85d2b839d3366 100644
--- a/libcxx/src/include/config_elast.h
+++ b/libcxx/src/include/config_elast.h
@@ -23,7 +23,7 @@
 #  define _LIBCPP_ELAST ELAST
 #elif defined(__LLVM_LIBC__)
 // No _LIBCPP_ELAST needed for LLVM libc
-#elif defined(_NEWLIB_VERSION)
+#elif _LIBCXX_LIBC_NEWLIB
 #  define _LIBCPP_ELAST __ELASTERROR
 #elif defined(__NuttX__)
 // No _LIBCPP_ELAST needed on NuttX
diff --git a/libcxx/src/locale.cpp b/libcxx/src/locale.cpp
index da735865c322c..0f05c8cee3940 100644
--- a/libcxx/src/locale.cpp
+++ b/libcxx/src/locale.cpp
@@ -933,7 +933,7 @@ const ctype<char>::mask* ctype<char>::classic_table() noexcept {
   return __pctype_func();
 #  elif defined(__EMSCRIPTEN__)
   return *__ctype_b_loc();
-#  elif defined(_NEWLIB_VERSION)
+#  elif _LIBCXX_LIBC_NEWLIB
   // Newlib has a 257-entry table in ctype_.c, where (char)0 starts at [1].
   return _ctype_ + 1;
 #  elif defined(_AIX)
diff --git a/libcxx/test/libcxx/system_reserved_names.gen.py b/libcxx/test/libcxx/system_reserved_names.gen.py
index a4f2928eda332..12c4a845f8db9 100644
--- a/libcxx/test/libcxx/system_reserved_names.gen.py
+++ b/libcxx/test/libcxx/system_reserved_names.gen.py
@@ -78,7 +78,7 @@
 
 // Test that libc++ doesn't use names that collide with FreeBSD system macros.
 // newlib and picolibc also define these macros
-#if !defined(__FreeBSD__) && !defined(_NEWLIB_VERSION)
+#if !defined(__FreeBSD__) && !_LIBCXX_LIBC_NEWLIB
 #  define __null_sentinel SYSTEM_RESERVED_NAME
 #  define __generic SYSTEM_RESERVED_NAME
 #endif
@@ -117,7 +117,7 @@
 #endif
 
 // Newlib & picolibc use __input as a parameter name of a64l & l64a
-#ifndef _NEWLIB_VERSION
+#if !_LIBCXX_LIBC_NEWLIB
 # define __input SYSTEM_RESERVED_NAME
 #endif
 #define __output SYSTEM_RESERVED_NAME
diff --git a/libcxx/test/std/diagnostics/syserr/syserr.errcat/syserr.errcat.objects/generic_category.pass.cpp b/libcxx/test/std/diagnostics/syserr/syserr.errcat/syserr.errcat.objects/generic_category.pass.cpp
index 5425203304014..ab277ad33ee40 100644
--- a/libcxx/test/std/diagnostics/syserr/syserr.errcat/syserr.errcat.objects/generic_category.pass.cpp
+++ b/libcxx/test/std/diagnostics/syserr/syserr.errcat/syserr.errcat.objects/generic_category.pass.cpp
@@ -48,7 +48,7 @@ int main(int, char**)
         // responds with an empty message, which we probably want to
         // treat as a failure code otherwise, but we can detect that
         // with the preprocessor.
-#if defined(_NEWLIB_VERSION)
+#if _LIBCXX_LIBC_NEWLIB
         const bool is_newlib = true;
 #else
         const bool is_newlib = false;
diff --git a/libcxx/test/std/diagnostics/syserr/syserr.errcat/syserr.errcat.objects/system_category.pass.cpp b/libcxx/test/std/diagnostics/syserr/syserr.errcat/syserr.errcat.objects/system_category.pass.cpp
index 255cbe75e2fa9..4fb117fe0554f 100644
--- a/libcxx/test/std/diagnostics/syserr/syserr.errcat/syserr.errcat.objects/system_category.pass.cpp
+++ b/libcxx/test/std/diagnostics/syserr/syserr.errcat/syserr.errcat.objects/system_category.pass.cpp
@@ -59,7 +59,7 @@ int main(int, char**) {
     // responds with an empty message, which we probably want to
     // treat as a failure code otherwise, but we can detect that
     // with the preprocessor.
-#if defined(_NEWLIB_VERSION)
+#if _LIBCXX_LIBC_NEWLIB
     const bool is_newlib = true;
 #else
     const bool is_newlib = false;
diff --git a/libcxx/test/support/platform_support.h b/libcxx/test/support/platform_support.h
index 99e60f60c5998..dfd8e7f55a0c5 100644
--- a/libcxx/test/support/platform_support.h
+++ b/libcxx/test/support/platform_support.h
@@ -48,7 +48,7 @@
 # include <string.h> // strverscmp
 #endif
 
-#if defined(_NEWLIB_VERSION) && defined(__STRICT_ANSI__)
+#if _LIBCXX_LIBC_NEWLIB && defined(__STRICT_ANSI__)
 // Newlib provides this, but in the header it's under __STRICT_ANSI__
 extern "C" {
   int mkstemp(char*);
diff --git a/libcxx/utils/ci/run-buildbot b/libcxx/utils/ci/run-buildbot
index d8b23be9a0323..9bd63d175a74c 100755
--- a/libcxx/utils/ci/run-buildbot
+++ b/libcxx/utils/ci/run-buildbot
@@ -230,6 +230,7 @@ function test-armv7m-picolibc() {
         -DLIBUNWIND_TEST_CONFIG="armv7m-picolibc-libunwind.cfg.in" \
         -DCMAKE_C_FLAGS="${flags}" \
         -DCMAKE_CXX_FLAGS="${flags}" \
+        -DRUNTIMES_USE_LIBC=picolibc \
         "${@}"
 
     step "Installing compiler-rt"
diff --git a/runtimes/cmake/Modules/HandleLibC.cmake b/runtimes/cmake/Modules/HandleLibC.cmake
index 51fbf04df7e3b..23f735aee6c02 100644
--- a/runtimes/cmake/Modules/HandleLibC.cmake
+++ b/runtimes/cmake/Modules/HandleLibC.cmake
@@ -10,10 +10,10 @@
 
 include_guard(GLOBAL)
 
-set(RUNTIMES_SUPPORTED_C_LIBRARIES system llvm-libc)
+set(RUNTIMES_SUPPORTED_C_LIBRARIES system llvm-libc picolibc newlib)
 set(RUNTIMES_USE_LIBC "system" CACHE STRING "Specify C library to use. Supported values are ${RUNTIMES_SUPPORTED_C_LIBRARIES}.")
 if (NOT "${RUNTIMES_USE_LIBC}" IN_LIST RUNTIMES_SUPPORTED_C_LIBRARIES)
-  message(FATAL_ERROR "Unsupported C library: '${RUNTIMES_CXX_ABI}'. Supported values are ${RUNTIMES_SUPPORTED_C_LIBRARIES}.")
+  message(FATAL_ERROR "Unsupported C library: '${RUNTIMES_USE_LIBC}'. Supported values are ${RUNTIMES_SUPPORTED_C_LIBRARIES}.")
 endif()
 
 # Link against a system-provided libc