diff --git a/changelog/6497.bugfix.rst b/changelog/6497.bugfix.rst
new file mode 100644
index 00000000000..d1e824b66bc
--- /dev/null
+++ b/changelog/6497.bugfix.rst
@@ -0,0 +1,4 @@
+Fix bug in the comparison of request key with cached key in fixture.
+
+A construct ``if key == cached_key:`` can fail either because ``==`` is explicitly disallowed, or for, e.g., NumPy arrays, where the result of ``a == b`` cannot generally be converted to `bool`.
+The implemented fix first compares using ``is``, and guards the subsequent ``==`` comparison against `TypeError` and `AttributeError`.
diff --git a/src/_pytest/fixtures.py b/src/_pytest/fixtures.py
index bae3d071674..b8976798750 100644
--- a/src/_pytest/fixtures.py
+++ b/src/_pytest/fixtures.py
@@ -894,7 +894,17 @@ def execute(self, request):
         cached_result = getattr(self, "cached_result", None)
         if cached_result is not None:
             result, cache_key, err = cached_result
-            if my_cache_key == cache_key:
+            # comparison with `==` can fail, e.g. for NumPy arrays, so we try `is`
+            # first and guard the subsequent `==` comparison
+            cache_valid = False
+            if my_cache_key is cache_key:
+                cache_valid = True
+            else:
+                try:
+                    cache_valid = bool(my_cache_key == cache_key)
+                except (TypeError, ValueError):
+                    pass
+            if cache_valid:
                 if err is not None:
                     _, val, tb = err
                     raise val.with_traceback(tb)