diff --git a/Doc/c-api/init.rst b/Doc/c-api/init.rst
index 3d18bb3f0b9..5736b83f211 100644
--- a/Doc/c-api/init.rst
+++ b/Doc/c-api/init.rst
@@ -376,6 +376,12 @@ Process-wide parameters
    The returned string points into static storage; the caller should not modify its
    value.
 
+   This function should not be called before :c:func:`Py_Initialize`, otherwise
+   it returns ``NULL``.
+
+   .. versionchanged:: 3.10
+      It now returns ``NULL`` if called before :c:func:`Py_Initialize`.
+
 
 .. c:function:: wchar_t* Py_GetPrefix()
 
@@ -389,6 +395,12 @@ Process-wide parameters
    script at build time.  The value is available to Python code as ``sys.prefix``.
    It is only useful on Unix.  See also the next function.
 
+   This function should not be called before :c:func:`Py_Initialize`, otherwise
+   it returns ``NULL``.
+
+   .. versionchanged:: 3.10
+      It now returns ``NULL`` if called before :c:func:`Py_Initialize`.
+
 
 .. c:function:: wchar_t* Py_GetExecPrefix()
 
@@ -424,6 +436,12 @@ Process-wide parameters
    while having :file:`/usr/local/plat` be a different filesystem for each
    platform.
 
+   This function should not be called before :c:func:`Py_Initialize`, otherwise
+   it returns ``NULL``.
+
+   .. versionchanged:: 3.10
+      It now returns ``NULL`` if called before :c:func:`Py_Initialize`.
+
 
 .. c:function:: wchar_t* Py_GetProgramFullPath()
 
@@ -437,6 +455,12 @@ Process-wide parameters
    static storage; the caller should not modify its value.  The value is available
    to Python code as ``sys.executable``.
 
+   This function should not be called before :c:func:`Py_Initialize`, otherwise
+   it returns ``NULL``.
+
+   .. versionchanged:: 3.10
+      It now returns ``NULL`` if called before :c:func:`Py_Initialize`.
+
 
 .. c:function:: wchar_t* Py_GetPath()
 
@@ -455,8 +479,14 @@ Process-wide parameters
    can be (and usually is) modified later to change the search path for loading
    modules.
 
+   This function should not be called before :c:func:`Py_Initialize`, otherwise
+   it returns ``NULL``.
+
    .. XXX should give the exact rules
 
+   .. versionchanged:: 3.10
+      It now returns ``NULL`` if called before :c:func:`Py_Initialize`.
+
 
 .. c:function::  void Py_SetPath(const wchar_t *)
 
@@ -638,6 +668,12 @@ Process-wide parameters
    :c:func:`Py_SetPythonHome`, or the value of the :envvar:`PYTHONHOME`
    environment variable if it is set.
 
+   This function should not be called before :c:func:`Py_Initialize`, otherwise
+   it returns ``NULL``.
+
+   .. versionchanged:: 3.10
+      It now returns ``NULL`` if called before :c:func:`Py_Initialize`.
+
 
 .. _threads:
 
diff --git a/Doc/c-api/init_config.rst b/Doc/c-api/init_config.rst
index edfeba5db7d..db7c1f43765 100644
--- a/Doc/c-api/init_config.rst
+++ b/Doc/c-api/init_config.rst
@@ -24,11 +24,15 @@ There are two kinds of configuration:
   environments variables are ignored, the LC_CTYPE locale is left unchanged and
   no signal handler is registred.
 
+The :c:func:`Py_RunMain` function can be used to write a customized Python
+program.
+
 See also :ref:`Initialization, Finalization, and Threads <initialization>`.
 
 .. seealso::
    :pep:`587` "Python Initialization Configuration".
 
+
 Example
 =======
 
@@ -532,7 +536,7 @@ PyConfig
 
       Default: ``NULL``.
 
-      Part of the :ref:`Path Configuration <init-path-config>` output.
+      Part of the :ref:`Python Path Configuration <init-path-config>` output.
 
    .. c:member:: wchar_t* base_executable
 
@@ -544,7 +548,7 @@ PyConfig
 
       Default: ``NULL``.
 
-      Part of the :ref:`Path Configuration <init-path-config>` output.
+      Part of the :ref:`Python Path Configuration <init-path-config>` output.
 
    .. c:member:: wchar_t* base_prefix
 
@@ -552,7 +556,7 @@ PyConfig
 
       Default: ``NULL``.
 
-      Part of the :ref:`Path Configuration <init-path-config>` output.
+      Part of the :ref:`Python Path Configuration <init-path-config>` output.
 
    .. c:member:: int buffered_stdio
 
@@ -634,7 +638,7 @@ PyConfig
 
       Default: ``NULL``.
 
-      Part of the :ref:`Path Configuration <init-path-config>` output.
+      Part of the :ref:`Python Path Configuration <init-path-config>` output.
 
    .. c:member:: wchar_t* executable
 
@@ -643,7 +647,7 @@ PyConfig
 
       Default: ``NULL``.
 
-      Part of the :ref:`Path Configuration <init-path-config>` output.
+      Part of the :ref:`Python Path Configuration <init-path-config>` output.
 
    .. c:member:: int faulthandler
 
@@ -726,7 +730,7 @@ PyConfig
 
       Default: ``NULL``.
 
-      Part of the :ref:`Path Configuration <init-path-config>` input.
+      Part of the :ref:`Python Path Configuration <init-path-config>` input.
 
    .. c:member:: int import_time
 
@@ -817,7 +821,7 @@ PyConfig
       Default: value of the ``PLATLIBDIR`` macro which is set at configure time
       by ``--with-platlibdir`` (default: ``"lib"``).
 
-      Part of the :ref:`Path Configuration <init-path-config>` input.
+      Part of the :ref:`Python Path Configuration <init-path-config>` input.
 
       .. versionadded:: 3.9
 
@@ -830,7 +834,7 @@ PyConfig
 
       Default: ``NULL``.
 
-      Part of the :ref:`Path Configuration <init-path-config>` input.
+      Part of the :ref:`Python Path Configuration <init-path-config>` input.
 
    .. c:member:: PyWideStringList module_search_paths
    .. c:member:: int module_search_paths_set
@@ -838,14 +842,14 @@ PyConfig
       Module search paths: :data:`sys.path`.
 
       If :c:member:`~PyConfig.module_search_paths_set` is equal to 0, the
-      function calculating the :ref:`Path Configuration <init-path-config>`
+      function calculating the :ref:`Python Path Configuration <init-path-config>`
       overrides the :c:member:`~PyConfig.module_search_paths` and sets
       :c:member:`~PyConfig.module_search_paths_set` to ``1``.
 
       Default: empty list (``module_search_paths``) and ``0``
       (``module_search_paths_set``).
 
-      Part of the :ref:`Path Configuration <init-path-config>` output.
+      Part of the :ref:`Python Path Configuration <init-path-config>` output.
 
    .. c:member:: int optimization_level
 
@@ -911,7 +915,7 @@ PyConfig
 
    .. c:member:: int pathconfig_warnings
 
-      On Unix, if non-zero, calculating the :ref:`Path Configuration
+      On Unix, if non-zero, calculating the :ref:`Python Path Configuration
       <init-path-config>` can log warnings into ``stderr``. If equals to 0,
       suppress these warnings.
 
@@ -919,7 +923,7 @@ PyConfig
 
       Default: ``1`` in Python mode, ``0`` in isolated mode.
 
-      Part of the :ref:`Path Configuration <init-path-config>` input.
+      Part of the :ref:`Python Path Configuration <init-path-config>` input.
 
    .. c:member:: wchar_t* prefix
 
@@ -928,7 +932,7 @@ PyConfig
 
       Default: ``NULL``.
 
-      Part of the :ref:`Path Configuration <init-path-config>` output.
+      Part of the :ref:`Python Path Configuration <init-path-config>` output.
 
    .. c:member:: wchar_t* program_name
 
@@ -946,7 +950,7 @@ PyConfig
 
       Default: ``NULL``.
 
-      Part of the :ref:`Path Configuration <init-path-config>` input.
+      Part of the :ref:`Python Path Configuration <init-path-config>` input.
 
    .. c:member:: wchar_t* pycache_prefix
 
@@ -1262,7 +1266,7 @@ and user site directory. The C standard streams (ex: ``stdout``) and the
 LC_CTYPE locale are left unchanged. Signal handlers are not installed.
 
 Configuration files are still used with this configuration. Set the
-:ref:`Path Configuration <init-path-config>` ("output fields") to ignore these
+:ref:`Python Path Configuration <init-path-config>` ("output fields") to ignore these
 configuration files and avoid the function computing the default path
 configuration.
 
@@ -1287,8 +1291,8 @@ and :ref:`Python UTF-8 Mode <utf8-mode>`
 
 .. _init-path-config:
 
-Path Configuration
-==================
+Python Path Configuration
+=========================
 
 :c:type:`PyConfig` contains multiple fields for the path configuration:
 
diff --git a/Doc/whatsnew/3.10.rst b/Doc/whatsnew/3.10.rst
index 95cdb06f997..76e11f0ddf0 100644
--- a/Doc/whatsnew/3.10.rst
+++ b/Doc/whatsnew/3.10.rst
@@ -493,6 +493,14 @@ Porting to Python 3.10
   ``unicodedata.ucnhash_CAPI`` has been moved to the internal C API.
   (Contributed by Victor Stinner in :issue:`42157`.)
 
+* :c:func:`Py_GetPath`, :c:func:`Py_GetPrefix`, :c:func:`Py_GetExecPrefix`,
+  :c:func:`Py_GetProgramFullPath`, :c:func:`Py_GetPythonHome` and
+  :c:func:`Py_GetProgramName` functions now return ``NULL`` if called before
+  :c:func:`Py_Initialize` (before Python is initialized). Use the new
+  :ref:`Python Initialization Configuration API <init-config>` to get the
+  :ref:`Python Path Configuration.  <init-path-config>`.
+  (Contributed by Victor Stinner in :issue:`42260`.)
+
 Deprecated
 ----------
 
diff --git a/Include/internal/pycore_initconfig.h b/Include/internal/pycore_initconfig.h
index d8400b1c42e..28cd57030e2 100644
--- a/Include/internal/pycore_initconfig.h
+++ b/Include/internal/pycore_initconfig.h
@@ -151,7 +151,9 @@ PyAPI_FUNC(void) _PyConfig_InitCompatConfig(PyConfig *config);
 extern PyStatus _PyConfig_Copy(
     PyConfig *config,
     const PyConfig *config2);
-extern PyStatus _PyConfig_InitPathConfig(PyConfig *config);
+extern PyStatus _PyConfig_InitPathConfig(
+    PyConfig *config,
+    int compute_path_config);
 extern PyStatus _PyConfig_Read(PyConfig *config, int compute_path_config);
 extern PyStatus _PyConfig_Write(const PyConfig *config,
     struct pyruntimestate *runtime);
diff --git a/Misc/NEWS.d/next/C API/2020-11-10-14-27-39.bpo-42260.-Br3Co.rst b/Misc/NEWS.d/next/C API/2020-11-10-14-27-39.bpo-42260.-Br3Co.rst
new file mode 100644
index 00000000000..e7b5a558fd4
--- /dev/null
+++ b/Misc/NEWS.d/next/C API/2020-11-10-14-27-39.bpo-42260.-Br3Co.rst	
@@ -0,0 +1,7 @@
+:c:func:`Py_GetPath`, :c:func:`Py_GetPrefix`, :c:func:`Py_GetExecPrefix`,
+:c:func:`Py_GetProgramFullPath`, :c:func:`Py_GetPythonHome` and
+:c:func:`Py_GetProgramName` functions now return ``NULL`` if called before
+:c:func:`Py_Initialize` (before Python is initialized). Use the new
+:ref:`Python Initialization Configuration API <init-config>` to get the
+:ref:`Python Path Configuration.  <init-path-config>`. Patch by Victor
+Stinner.
diff --git a/Python/initconfig.c b/Python/initconfig.c
index 11db4a3ef59..1fcc3600aa4 100644
--- a/Python/initconfig.c
+++ b/Python/initconfig.c
@@ -2069,8 +2069,8 @@ config_read(PyConfig *config, int compute_path_config)
         }
     }
 
-    if (compute_path_config && config->_install_importlib) {
-        status = _PyConfig_InitPathConfig(config);
+    if (config->_install_importlib) {
+        status = _PyConfig_InitPathConfig(config, compute_path_config);
         if (_PyStatus_EXCEPTION(status)) {
             return status;
         }
diff --git a/Python/pathconfig.c b/Python/pathconfig.c
index 12a684a66b7..470aba75bea 100644
--- a/Python/pathconfig.c
+++ b/Python/pathconfig.c
@@ -332,7 +332,8 @@ config_init_module_search_paths(PyConfig *config, _PyPathConfig *pathconfig)
    - _PyPathConfig_Calculate()
 */
 static PyStatus
-pathconfig_calculate(_PyPathConfig *pathconfig, const PyConfig *config)
+pathconfig_init(_PyPathConfig *pathconfig, const PyConfig *config,
+                int compute_path_config)
 {
     PyStatus status;
 
@@ -349,12 +350,9 @@ pathconfig_calculate(_PyPathConfig *pathconfig, const PyConfig *config)
         goto done;
     }
 
-    if (_Py_path_config.module_search_path == NULL) {
+    if (compute_path_config) {
         status = _PyPathConfig_Calculate(pathconfig, config);
     }
-    else {
-        /* Py_SetPath() has been called: avoid _PyPathConfig_Calculate() */
-    }
 
 done:
     PyMem_SetAllocator(PYMEM_DOMAIN_RAW, &old_alloc);
@@ -363,17 +361,19 @@ done:
 
 
 static PyStatus
-config_calculate_pathconfig(PyConfig *config)
+config_init_pathconfig(PyConfig *config, int compute_path_config)
 {
     _PyPathConfig pathconfig = _PyPathConfig_INIT;
     PyStatus status;
 
-    status = pathconfig_calculate(&pathconfig, config);
+    status = pathconfig_init(&pathconfig, config, compute_path_config);
     if (_PyStatus_EXCEPTION(status)) {
         goto done;
     }
 
-    if (!config->module_search_paths_set) {
+    if (!config->module_search_paths_set
+        && pathconfig.module_search_path != NULL)
+    {
         status = config_init_module_search_paths(config, &pathconfig);
         if (_PyStatus_EXCEPTION(status)) {
             goto done;
@@ -381,7 +381,7 @@ config_calculate_pathconfig(PyConfig *config)
     }
 
 #define COPY_ATTR(PATH_ATTR, CONFIG_ATTR) \
-        if (config->CONFIG_ATTR == NULL) { \
+        if (config->CONFIG_ATTR == NULL && pathconfig.PATH_ATTR != NULL) { \
             if (copy_wstr(&config->CONFIG_ATTR, pathconfig.PATH_ATTR) < 0) { \
                 goto no_memory; \
             } \
@@ -427,7 +427,7 @@ done:
 
 
 PyStatus
-_PyConfig_InitPathConfig(PyConfig *config)
+_PyConfig_InitPathConfig(PyConfig *config, int compute_path_config)
 {
     /* Do we need to calculate the path? */
     if (!config->module_search_paths_set
@@ -435,26 +435,26 @@ _PyConfig_InitPathConfig(PyConfig *config)
         || config->prefix == NULL
         || config->exec_prefix == NULL)
     {
-        PyStatus status = config_calculate_pathconfig(config);
+        PyStatus status = config_init_pathconfig(config, compute_path_config);
         if (_PyStatus_EXCEPTION(status)) {
             return status;
         }
     }
 
-    if (config->base_prefix == NULL) {
+    if (config->base_prefix == NULL && config->prefix != NULL) {
         if (copy_wstr(&config->base_prefix, config->prefix) < 0) {
             return _PyStatus_NO_MEMORY();
         }
     }
 
-    if (config->base_exec_prefix == NULL) {
+    if (config->base_exec_prefix == NULL && config->exec_prefix != NULL) {
         if (copy_wstr(&config->base_exec_prefix,
                       config->exec_prefix) < 0) {
             return _PyStatus_NO_MEMORY();
         }
     }
 
-    if (config->base_executable == NULL) {
+    if (config->base_executable == NULL && config->executable != NULL) {
         if (copy_wstr(&config->base_executable,
                       config->executable) < 0) {
             return _PyStatus_NO_MEMORY();
@@ -465,53 +465,6 @@ _PyConfig_InitPathConfig(PyConfig *config)
 }
 
 
-static PyStatus
-pathconfig_global_read(_PyPathConfig *pathconfig)
-{
-    PyConfig config;
-    _PyConfig_InitCompatConfig(&config);
-
-    /* Call _PyConfig_InitPathConfig() */
-    PyStatus status = PyConfig_Read(&config);
-    if (_PyStatus_EXCEPTION(status)) {
-        goto done;
-    }
-
-    status = pathconfig_set_from_config(pathconfig, &config);
-
-done:
-    PyConfig_Clear(&config);
-    return status;
-}
-
-
-static void
-pathconfig_global_init(void)
-{
-    PyStatus status;
-
-    if (_Py_path_config.module_search_path == NULL) {
-        status = pathconfig_global_read(&_Py_path_config);
-        if (_PyStatus_EXCEPTION(status)) {
-            Py_ExitStatusException(status);
-        }
-    }
-    else {
-        /* Global configuration already initialized */
-    }
-
-    assert(_Py_path_config.program_full_path != NULL);
-    assert(_Py_path_config.prefix != NULL);
-    assert(_Py_path_config.exec_prefix != NULL);
-    assert(_Py_path_config.module_search_path != NULL);
-    assert(_Py_path_config.program_name != NULL);
-    /* home can be NULL */
-#ifdef MS_WINDOWS
-    assert(_Py_path_config.base_executable != NULL);
-#endif
-}
-
-
 /* External interface */
 
 static void _Py_NO_RETURN
@@ -531,23 +484,17 @@ Py_SetPath(const wchar_t *path)
     PyMemAllocatorEx old_alloc;
     _PyMem_SetDefaultAllocator(PYMEM_DOMAIN_RAW, &old_alloc);
 
-    /* Getting the program full path calls pathconfig_global_init() */
-    wchar_t *program_full_path = _PyMem_RawWcsdup(Py_GetProgramFullPath());
-
-    PyMem_RawFree(_Py_path_config.program_full_path);
     PyMem_RawFree(_Py_path_config.prefix);
     PyMem_RawFree(_Py_path_config.exec_prefix);
     PyMem_RawFree(_Py_path_config.module_search_path);
 
-    _Py_path_config.program_full_path = program_full_path;
     _Py_path_config.prefix = _PyMem_RawWcsdup(L"");
     _Py_path_config.exec_prefix = _PyMem_RawWcsdup(L"");
     _Py_path_config.module_search_path = _PyMem_RawWcsdup(path);
 
     PyMem_SetAllocator(PYMEM_DOMAIN_RAW, &old_alloc);
 
-    if (_Py_path_config.program_full_path == NULL
-        || _Py_path_config.prefix == NULL
+    if (_Py_path_config.prefix == NULL
         || _Py_path_config.exec_prefix == NULL
         || _Py_path_config.module_search_path == NULL)
     {
@@ -621,7 +568,6 @@ _Py_SetProgramFullPath(const wchar_t *program_full_path)
 wchar_t *
 Py_GetPath(void)
 {
-    pathconfig_global_init();
     return _Py_path_config.module_search_path;
 }
 
@@ -629,7 +575,6 @@ Py_GetPath(void)
 wchar_t *
 Py_GetPrefix(void)
 {
-    pathconfig_global_init();
     return _Py_path_config.prefix;
 }
 
@@ -637,7 +582,6 @@ Py_GetPrefix(void)
 wchar_t *
 Py_GetExecPrefix(void)
 {
-    pathconfig_global_init();
     return _Py_path_config.exec_prefix;
 }
 
@@ -645,7 +589,6 @@ Py_GetExecPrefix(void)
 wchar_t *
 Py_GetProgramFullPath(void)
 {
-    pathconfig_global_init();
     return _Py_path_config.program_full_path;
 }
 
@@ -653,7 +596,6 @@ Py_GetProgramFullPath(void)
 wchar_t*
 Py_GetPythonHome(void)
 {
-    pathconfig_global_init();
     return _Py_path_config.home;
 }
 
@@ -661,7 +603,6 @@ Py_GetPythonHome(void)
 wchar_t *
 Py_GetProgramName(void)
 {
-    pathconfig_global_init();
     return _Py_path_config.program_name;
 }
 
diff --git a/Python/pylifecycle.c b/Python/pylifecycle.c
index 609e0a42e4d..93bce49b63d 100644
--- a/Python/pylifecycle.c
+++ b/Python/pylifecycle.c
@@ -1039,7 +1039,7 @@ init_interp_main(PyThreadState *tstate)
     }
 
     // Compute the path configuration
-    status = _PyConfig_InitPathConfig(&interp->config);
+    status = _PyConfig_InitPathConfig(&interp->config, 1);
     if (_PyStatus_EXCEPTION(status)) {
         return status;
     }