diff --git a/doc/source/whatsnew/v0.21.0.txt b/doc/source/whatsnew/v0.21.0.txt
index 7fbf2533428dc4..364b10a616462d 100644
--- a/doc/source/whatsnew/v0.21.0.txt
+++ b/doc/source/whatsnew/v0.21.0.txt
@@ -109,6 +109,19 @@ For example:
     # the following is now equivalent
     df.drop(columns=['B', 'C'])
 
+``rename`` now also accepts axis keyword
+^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^
+
+The :meth:`~DataFrame.rename` method has gained the ``axis`` keyword as an
+alternative to specify the ``axis`` to target (:issue:`12392`).
+
+.. ipython:: 
+
+    df = pd.DataFrame({"A": [1, 2, 3], "B": [4, 5, 6]})
+    df.rename(str.lower, axis='columns')
+
+The ``.rename(columns=str.lower)`` style continues to work as before.
+
 .. _whatsnew_0210.enhancements.categorical_dtype:
 
 ``CategoricalDtype`` for specifying categoricals
diff --git a/pandas/core/frame.py b/pandas/core/frame.py
index 142ccf1f034bc6..0d7e7ee8d7c758 100644
--- a/pandas/core/frame.py
+++ b/pandas/core/frame.py
@@ -2904,7 +2904,28 @@ def reindex_axis(self, labels, axis=0, method=None, level=None, copy=True,
                                         limit=limit, fill_value=fill_value)
 
     @Appender(_shared_docs['rename'] % _shared_doc_kwargs)
-    def rename(self, index=None, columns=None, **kwargs):
+    def rename(self, *args, index=None, columns=None, **kwargs):
+        nargs = len(args)
+        if 'axis' in kwargs and (index is not None or columns is not None):
+            raise TypeError("Cannot specify 'index' or 'columns' and 'axis' at"
+                            " the same time. Specify either\n"
+                            "\t.rename(mapping, axis=axis), or\n"
+                            "\t.rename(index=index, columns=columns)")
+        if 'axis' in kwargs and nargs > 1:
+            raise TypeError("Cannot specify 'index', 'axis', and 'columns' at "
+                            "the same time.")
+        if nargs > 2:
+            raise TypeError("Too many positional arguments")
+
+        if nargs and index is not None:
+            raise TypeError("rename() got multiple arguments for argumnet "
+                            "'index'")
+
+        if index is None and nargs:
+            index = args[0]
+        if columns is None and nargs > 1:
+            columns = args[1]
+
         return super(DataFrame, self).rename(index=index, columns=columns,
                                              **kwargs)
 
diff --git a/pandas/core/generic.py b/pandas/core/generic.py
index 942a9ff2790927..d3d796650dfbb9 100644
--- a/pandas/core/generic.py
+++ b/pandas/core/generic.py
@@ -807,11 +807,20 @@ def swaplevel(self, i=-2, j=-1, axis=0):
     @Appender(_shared_docs['rename'] % dict(axes='axes keywords for this'
                                             ' object', klass='NDFrame'))
     def rename(self, *args, **kwargs):
-
         axes, kwargs = self._construct_axes_from_arguments(args, kwargs)
         copy = kwargs.pop('copy', True)
         inplace = kwargs.pop('inplace', False)
         level = kwargs.pop('level', None)
+        axis = kwargs.pop("axis", None)
+
+        if axis:
+            # At this point, we know the call was
+            # rename(fn, axis=axis), so axes is always
+            # {index: op, columns: None}
+            axis = self._get_axis_name(axis)
+            op = axes['index']
+            axes['index'] = None
+            axes[axis] = op
 
         if kwargs:
             raise TypeError('rename() got an unexpected keyword '
diff --git a/pandas/tests/frame/test_alter_axes.py b/pandas/tests/frame/test_alter_axes.py
index 27906838abb2de..3fe97ddea2e023 100644
--- a/pandas/tests/frame/test_alter_axes.py
+++ b/pandas/tests/frame/test_alter_axes.py
@@ -837,6 +837,66 @@ def test_rename_objects(self):
         assert 'FOO' in renamed
         assert 'foo' not in renamed
 
+    def test_rename_columns(self):
+        df = pd.DataFrame({"A": [1, 2], "B": [1, 2]}, index=['X', 'Y'])
+        expected = pd.DataFrame({"a": [1, 2], "b": [1, 2]}, index=['X', 'Y'])
+
+        result = df.rename(str.lower, axis=1)
+        assert_frame_equal(result, expected)
+
+        result = df.rename(str.lower, axis='columns')
+        assert_frame_equal(result, expected)
+
+        result = df.rename({"A": 'a', 'B': 'b'}, axis=1)
+        assert_frame_equal(result, expected)
+
+        result = df.rename({"A": 'a', 'B': 'b'}, axis='columns')
+        assert_frame_equal(result, expected)
+
+        # Index
+        expected = pd.DataFrame({"A": [1, 2], "B": [1, 2]}, index=['x', 'y'])
+        result = df.rename(str.lower, axis=0)
+        assert_frame_equal(result, expected)
+
+        result = df.rename(str.lower, axis='index')
+        assert_frame_equal(result, expected)
+
+        result = df.rename({'X': 'x', 'Y': 'y'}, axis=0)
+        assert_frame_equal(result, expected)
+
+        result = df.rename({'X': 'x', 'Y': 'y'}, axis='index')
+        assert_frame_equal(result, expected)
+
+    def test_rename_raises(self):
+        df = pd.DataFrame({"A": [1, 2], "B": [1, 2]}, index=['0', '1'])
+
+        # Named target and axis
+        with tm.assert_raises_regex(TypeError, None):
+            df.rename(index=str.lower, axis=1)
+
+        with tm.assert_raises_regex(TypeError, None):
+            df.rename(index=str.lower, axis='columns')
+
+        with tm.assert_raises_regex(TypeError, None):
+            df.rename(index=str.lower, axis=0)
+
+        with tm.assert_raises_regex(TypeError, None):
+            df.rename(index=str.lower, axis='columns')
+
+        with tm.assert_raises_regex(TypeError, None):
+            df.rename(columns=str.lower, axis='columns')
+
+        # Multiple targets and axis
+        with tm.assert_raises_regex(TypeError, None):
+            df.rename(str.lower, str.lower, axis='columns')
+
+        # Too many targets
+        with tm.assert_raises_regex(TypeError, None):
+            df.rename(str.lower, str.lower, str.lower)
+
+        with tm.assert_raises_regex(TypeError, None):
+            df.rename(str.lower, index=str.lower)
+
     def test_assign_columns(self):
         self.frame['hi'] = 'there'