diff --git a/doc/source/whatsnew/v2.0.2.rst b/doc/source/whatsnew/v2.0.2.rst
index b6c6df8424ef1..5c3187cda15ae 100644
--- a/doc/source/whatsnew/v2.0.2.rst
+++ b/doc/source/whatsnew/v2.0.2.rst
@@ -13,6 +13,7 @@ including other versions of pandas.
 
 Fixed regressions
 ~~~~~~~~~~~~~~~~~
+- Fixed regression in :meth:`DataFrame.loc` losing :class:`MultiIndex` name when enlarging object (:issue:`53053`)
 -
 
 .. ---------------------------------------------------------------------------
diff --git a/pandas/core/frame.py b/pandas/core/frame.py
index 636267e54027f..928ebdd39f984 100644
--- a/pandas/core/frame.py
+++ b/pandas/core/frame.py
@@ -9914,7 +9914,12 @@ def _append(
                     "or if the Series has a name"
                 )
 
-            index = Index([other.name], name=self.index.name)
+            index = Index(
+                [other.name],
+                name=self.index.names
+                if isinstance(self.index, MultiIndex)
+                else self.index.name,
+            )
             row_df = other.to_frame().T
             # infer_objects is needed for
             #  test_append_empty_frame_to_series_with_dateutil_tz
diff --git a/pandas/tests/indexing/multiindex/test_setitem.py b/pandas/tests/indexing/multiindex/test_setitem.py
index 27b4a4be73032..e6f44359a1a62 100644
--- a/pandas/tests/indexing/multiindex/test_setitem.py
+++ b/pandas/tests/indexing/multiindex/test_setitem.py
@@ -479,6 +479,21 @@ def test_setitem_new_column_all_na(self):
         df["new"] = s
         assert df["new"].isna().all()
 
+    def test_setitem_enlargement_keep_index_names(self):
+        # GH#53053
+        mi = MultiIndex.from_tuples([(1, 2, 3)], names=["i1", "i2", "i3"])
+        df = DataFrame(data=[[10, 20, 30]], index=mi, columns=["A", "B", "C"])
+        df.loc[(0, 0, 0)] = df.loc[(1, 2, 3)]
+        mi_expected = MultiIndex.from_tuples(
+            [(1, 2, 3), (0, 0, 0)], names=["i1", "i2", "i3"]
+        )
+        expected = DataFrame(
+            data=[[10, 20, 30], [10, 20, 30]],
+            index=mi_expected,
+            columns=["A", "B", "C"],
+        )
+        tm.assert_frame_equal(df, expected)
+
 
 @td.skip_array_manager_invalid_test  # df["foo"] select multiple columns -> .values
 # is not a view