diff --git a/Lib/test/test_getpath.py b/Lib/test/test_getpath.py
index 7e5c4a3d14d..f86df9d0d03 100644
--- a/Lib/test/test_getpath.py
+++ b/Lib/test/test_getpath.py
@@ -832,6 +832,37 @@ def test_explicitly_set_stdlib_dir(self):
         actual = getpath(ns, expected)
         self.assertEqual(expected, actual)
 
+    def test_PYTHONHOME_in_venv(self):
+        "Make sure prefix/exec_prefix still point to the venv if PYTHONHOME was used."
+        ns = MockPosixNamespace(
+            argv0="/venv/bin/python",
+            PREFIX="/usr",
+            ENV_PYTHONHOME="/pythonhome",
+        )
+        # Setup venv
+        ns.add_known_xfile("/venv/bin/python")
+        ns.add_known_file("/venv/pyvenv.cfg", [
+            r"home = /usr/bin"
+        ])
+        # Seutup PYTHONHOME
+        ns.add_known_file("/pythonhome/lib/python9.8/os.py")
+        ns.add_known_dir("/pythonhome/lib/python9.8/lib-dynload")
+
+        expected = dict(
+            executable="/venv/bin/python",
+            prefix="/venv",
+            exec_prefix="/venv",
+            base_prefix="/pythonhome",
+            base_exec_prefix="/pythonhome",
+            module_search_paths_set=1,
+            module_search_paths=[
+                "/pythonhome/lib/python98.zip",
+                "/pythonhome/lib/python9.8",
+                "/pythonhome/lib/python9.8/lib-dynload",
+            ],
+        )
+        actual = getpath(ns, expected)
+        self.assertEqual(expected, actual)
 
 # ******************************************************************************
 
diff --git a/Modules/getpath.py b/Modules/getpath.py
index b14f985a0d5..c34101e7208 100644
--- a/Modules/getpath.py
+++ b/Modules/getpath.py
@@ -344,9 +344,10 @@ def search_up(prefix, *landmarks, test=isfile):
 
 venv_prefix = None
 
-# Calling Py_SetPythonHome(), Py_SetPath() or
-# setting $PYTHONHOME will override venv detection.
-if not home and not py_setpath:
+# Calling Py_SetPath() will override venv detection.
+# Calling Py_SetPythonHome() or setting $PYTHONHOME will override the 'home' key
+# specified in pyvenv.cfg.
+if not py_setpath:
     try:
         # prefix2 is just to avoid calculating dirname again later,
         # as the path in venv_prefix is the more common case.
@@ -370,6 +371,9 @@ def search_up(prefix, *landmarks, test=isfile):
     for line in pyvenvcfg:
         key, had_equ, value = line.partition('=')
         if had_equ and key.strip().lower() == 'home':
+            # If PYTHONHOME was set, ignore 'home' from pyvenv.cfg.
+            if home:
+                break
             # Override executable_dir/real_executable_dir with the value from 'home'.
             # These values may be later used to calculate prefix/base_prefix, if a more
             # reliable source — like the runtime library (libpython) path — isn't available.