diff --git a/doc/source/whatsnew/v1.0.0.rst b/doc/source/whatsnew/v1.0.0.rst
index b93856db6ba8d0..a646c4aa03687d 100644
--- a/doc/source/whatsnew/v1.0.0.rst
+++ b/doc/source/whatsnew/v1.0.0.rst
@@ -614,6 +614,7 @@ or ``matplotlib.Axes.plot``. See :ref:`plotting.formatters` for more.
 - Changed :meth:`Timedelta.resolution` to match the behavior of the standard library ``datetime.timedelta.resolution``, for the old behavior, use :meth:`Timedelta.resolution_string` (:issue:`26839`)
 - Removed previously deprecated :attr:`Timestamp.weekday_name`, :attr:`DatetimeIndex.weekday_name`, and :attr:`Series.dt.weekday_name` (:issue:`18164`)
 - Removed previously deprecated ``errors`` argument in :meth:`Timestamp.tz_localize`, :meth:`DatetimeIndex.tz_localize`, and :meth:`Series.tz_localize` (:issue:`22644`)
+- :meth:`Series.set_axis` and :meth:`DataFrame.set_axis` now require "labels" as the first argument and "axis" as an optional named parameter (:issue:`30089`)
 -
 
 .. _whatsnew_1000.performance:
diff --git a/pandas/core/generic.py b/pandas/core/generic.py
index bcc742e731110e..3e41721b65f5d3 100644
--- a/pandas/core/generic.py
+++ b/pandas/core/generic.py
@@ -633,17 +633,6 @@ def set_axis(self, labels, axis=0, inplace=False):
         1  2   5
         2  3   6
         """
-        if is_scalar(labels):
-            warnings.warn(
-                'set_axis now takes "labels" as first argument, and '
-                '"axis" as named parameter. The old form, with "axis" as '
-                'first parameter and "labels" as second, is still supported '
-                "but will be deprecated in a future version of pandas.",
-                FutureWarning,
-                stacklevel=2,
-            )
-            labels, axis = axis, labels
-
         if inplace:
             setattr(self, self._get_axis_name(axis), labels)
         else:
diff --git a/pandas/tests/frame/test_alter_axes.py b/pandas/tests/frame/test_alter_axes.py
index b52f24f9e06f12..48b373d9c7901e 100644
--- a/pandas/tests/frame/test_alter_axes.py
+++ b/pandas/tests/frame/test_alter_axes.py
@@ -1548,21 +1548,3 @@ def test_set_axis_inplace(self):
         for axis in 3, "foo":
             with pytest.raises(ValueError, match="No axis named"):
                 df.set_axis(list("abc"), axis=axis)
-
-    def test_set_axis_prior_to_deprecation_signature(self):
-        df = DataFrame(
-            {"A": [1.1, 2.2, 3.3], "B": [5.0, 6.1, 7.2], "C": [4.4, 5.5, 6.6]},
-            index=[2010, 2011, 2012],
-        )
-
-        expected = {0: df.copy(), 1: df.copy()}
-        expected[0].index = list("abc")
-        expected[1].columns = list("abc")
-        expected["index"] = expected[0]
-        expected["columns"] = expected[1]
-
-        # old signature
-        for axis in expected:
-            with tm.assert_produces_warning(FutureWarning):
-                result = df.set_axis(axis, list("abc"), inplace=False)
-            tm.assert_frame_equal(result, expected[axis])
diff --git a/pandas/tests/series/test_alter_axes.py b/pandas/tests/series/test_alter_axes.py
index 7a24a45b4b6c2e..9e1bae84691380 100644
--- a/pandas/tests/series/test_alter_axes.py
+++ b/pandas/tests/series/test_alter_axes.py
@@ -322,17 +322,6 @@ def test_set_axis_inplace(self):
             with pytest.raises(ValueError, match="No axis named"):
                 s.set_axis(list("abcd"), axis=axis, inplace=False)
 
-    def test_set_axis_prior_to_deprecation_signature(self):
-        s = Series(np.arange(4), index=[1, 3, 5, 7], dtype="int64")
-
-        expected = s.copy()
-        expected.index = list("abcd")
-
-        for axis in [0, "index"]:
-            with tm.assert_produces_warning(FutureWarning):
-                result = s.set_axis(0, list("abcd"), inplace=False)
-            tm.assert_series_equal(result, expected)
-
     def test_reset_index_drop_errors(self):
         #  GH 20925