diff --git a/tools/FindPythonLibsNew.cmake b/tools/FindPythonLibsNew.cmake
index a035428f8..a5a628fd7 100644
--- a/tools/FindPythonLibsNew.cmake
+++ b/tools/FindPythonLibsNew.cmake
@@ -151,26 +151,36 @@ if(NOT _PYTHON_SUCCESS MATCHES 0)
   return()
 endif()
 
+# Can manually set values when cross-compiling
+macro(_PYBIND11_GET_IF_UNDEF lst index name)
+  if(NOT DEFINED "${name}")
+    list(GET "${lst}" "${index}" "${name}")
+  endif()
+endmacro()
+
 # Convert the process output into a list
 if(WIN32)
   string(REGEX REPLACE "\\\\" "/" _PYTHON_VALUES ${_PYTHON_VALUES})
 endif()
 string(REGEX REPLACE ";" "\\\\;" _PYTHON_VALUES ${_PYTHON_VALUES})
 string(REGEX REPLACE "\n" ";" _PYTHON_VALUES ${_PYTHON_VALUES})
-list(GET _PYTHON_VALUES 0 _PYTHON_VERSION_LIST)
-list(GET _PYTHON_VALUES 1 PYTHON_PREFIX)
-list(GET _PYTHON_VALUES 2 PYTHON_INCLUDE_DIR)
-list(GET _PYTHON_VALUES 3 PYTHON_SITE_PACKAGES)
-list(GET _PYTHON_VALUES 4 PYTHON_MODULE_EXTENSION)
-list(GET _PYTHON_VALUES 5 PYTHON_IS_DEBUG)
-list(GET _PYTHON_VALUES 6 PYTHON_SIZEOF_VOID_P)
-list(GET _PYTHON_VALUES 7 PYTHON_LIBRARY_SUFFIX)
-list(GET _PYTHON_VALUES 8 PYTHON_LIBDIR)
-list(GET _PYTHON_VALUES 9 PYTHON_MULTIARCH)
+_pybind11_get_if_undef(_PYTHON_VALUES 0 _PYTHON_VERSION_LIST)
+_pybind11_get_if_undef(_PYTHON_VALUES 1 PYTHON_PREFIX)
+_pybind11_get_if_undef(_PYTHON_VALUES 2 PYTHON_INCLUDE_DIR)
+_pybind11_get_if_undef(_PYTHON_VALUES 3 PYTHON_SITE_PACKAGES)
+_pybind11_get_if_undef(_PYTHON_VALUES 4 PYTHON_MODULE_EXTENSION)
+_pybind11_get_if_undef(_PYTHON_VALUES 5 PYTHON_IS_DEBUG)
+_pybind11_get_if_undef(_PYTHON_VALUES 6 PYTHON_SIZEOF_VOID_P)
+_pybind11_get_if_undef(_PYTHON_VALUES 7 PYTHON_LIBRARY_SUFFIX)
+_pybind11_get_if_undef(_PYTHON_VALUES 8 PYTHON_LIBDIR)
+_pybind11_get_if_undef(_PYTHON_VALUES 9 PYTHON_MULTIARCH)
 
 # Make sure the Python has the same pointer-size as the chosen compiler
 # Skip if CMAKE_SIZEOF_VOID_P is not defined
-if(CMAKE_SIZEOF_VOID_P AND (NOT "${PYTHON_SIZEOF_VOID_P}" STREQUAL "${CMAKE_SIZEOF_VOID_P}"))
+# This should be skipped for (non-Apple) cross-compiles (like EMSCRIPTEN)
+if(NOT CMAKE_CROSSCOMPILING
+   AND CMAKE_SIZEOF_VOID_P
+   AND (NOT "${PYTHON_SIZEOF_VOID_P}" STREQUAL "${CMAKE_SIZEOF_VOID_P}"))
   if(PythonLibsNew_FIND_REQUIRED)
     math(EXPR _PYTHON_BITS "${PYTHON_SIZEOF_VOID_P} * 8")
     math(EXPR _CMAKE_BITS "${CMAKE_SIZEOF_VOID_P} * 8")