diff --git a/doc/source/whatsnew/v1.2.0.rst b/doc/source/whatsnew/v1.2.0.rst
index 407e8ba029ada..7460043d8c89e 100644
--- a/doc/source/whatsnew/v1.2.0.rst
+++ b/doc/source/whatsnew/v1.2.0.rst
@@ -281,7 +281,7 @@ ExtensionArray
 
 Other
 ^^^^^
--
+- Bug in :meth:`DataFrame.replace` and :meth:`Series.replace` incorrectly raising ``AssertionError`` instead of ``ValueError`` when invalid parameter combinations are passed (:issue:`36045`)
 -
 
 .. ---------------------------------------------------------------------------
diff --git a/pandas/core/generic.py b/pandas/core/generic.py
index 3bad2d6dd18b9..ce2625f3ec15d 100644
--- a/pandas/core/generic.py
+++ b/pandas/core/generic.py
@@ -6179,8 +6179,8 @@ def replace(
         self,
         to_replace=None,
         value=None,
-        inplace=False,
-        limit=None,
+        inplace: bool_t = False,
+        limit: Optional[int] = None,
         regex=False,
         method="pad",
     ):
@@ -6256,7 +6256,7 @@ def replace(
             If True, in place. Note: this will modify any
             other views on this object (e.g. a column from a DataFrame).
             Returns the caller if this is True.
-        limit : int, default None
+        limit : int or None, default None
             Maximum size gap to forward or backward fill.
         regex : bool or same types as `to_replace`, default False
             Whether to interpret `to_replace` and/or `value` as regular
@@ -6490,7 +6490,7 @@ def replace(
 
         inplace = validate_bool_kwarg(inplace, "inplace")
         if not is_bool(regex) and to_replace is not None:
-            raise AssertionError("'to_replace' must be 'None' if 'regex' is not a bool")
+            raise ValueError("'to_replace' must be 'None' if 'regex' is not a bool")
 
         if value is None:
             # passing a single value that is scalar like
@@ -6550,12 +6550,14 @@ def replace(
 
             # need a non-zero len on all axes
             if not self.size:
-                return self
+                if inplace:
+                    return
+                return self.copy()
 
             if is_dict_like(to_replace):
                 if is_dict_like(value):  # {'A' : NA} -> {'A' : 0}
                     # Note: Checking below for `in foo.keys()` instead of
-                    #  `in foo`is needed for when we have a Series and not dict
+                    #  `in foo` is needed for when we have a Series and not dict
                     mapping = {
                         col: (to_replace[col], value[col])
                         for col in to_replace.keys()
diff --git a/pandas/tests/series/methods/test_replace.py b/pandas/tests/series/methods/test_replace.py
index f78a28c66e946..ccaa005369a1c 100644
--- a/pandas/tests/series/methods/test_replace.py
+++ b/pandas/tests/series/methods/test_replace.py
@@ -397,6 +397,29 @@ def test_replace_invalid_to_replace(self):
         with pytest.raises(TypeError, match=msg):
             series.replace(lambda x: x.strip())
 
+    @pytest.mark.parametrize("frame", [False, True])
+    def test_replace_nonbool_regex(self, frame):
+        obj = pd.Series(["a", "b", "c "])
+        if frame:
+            obj = obj.to_frame()
+
+        msg = "'to_replace' must be 'None' if 'regex' is not a bool"
+        with pytest.raises(ValueError, match=msg):
+            obj.replace(to_replace=["a"], regex="foo")
+
+    @pytest.mark.parametrize("frame", [False, True])
+    def test_replace_empty_copy(self, frame):
+        obj = pd.Series([], dtype=np.float64)
+        if frame:
+            obj = obj.to_frame()
+
+        res = obj.replace(4, 5, inplace=True)
+        assert res is None
+
+        res = obj.replace(4, 5, inplace=False)
+        tm.assert_equal(res, obj)
+        assert res is not obj
+
     def test_replace_only_one_dictlike_arg(self):
         # GH#33340