diff --git a/asv_bench/benchmarks/indexing.py b/asv_bench/benchmarks/indexing.py
index 74e0a3a434cde..4fd91c8aafe4b 100644
--- a/asv_bench/benchmarks/indexing.py
+++ b/asv_bench/benchmarks/indexing.py
@@ -358,6 +358,14 @@ def time_assign_with_setitem(self):
         for i in range(100):
             self.df[i] = np.random.randn(self.N)
 
+    def time_assign_list_like_with_setitem(self):
+        np.random.seed(1234)
+        self.df[list(range(100))] = np.random.randn(self.N, 100)
+
+    def time_assign_list_of_columns_concat(self):
+        df = DataFrame(np.random.randn(self.N, 100))
+        concat([self.df, df], axis=1)
+
 
 class ChainIndexing:
 
diff --git a/doc/source/whatsnew/v1.2.0.rst b/doc/source/whatsnew/v1.2.0.rst
index 24db70481c136..270de56a000a0 100644
--- a/doc/source/whatsnew/v1.2.0.rst
+++ b/doc/source/whatsnew/v1.2.0.rst
@@ -548,6 +548,7 @@ Performance improvements
 - Performance improvement in :meth:`Series.astype` and :meth:`DataFrame.astype` for :class:`Categorical` (:issue:`8628`)
 - Performance improvement in :meth:`DataFrame.groupby` for ``float`` ``dtype`` (:issue:`28303`), changes of the underlying hash-function can lead to changes in float based indexes sort ordering for ties (e.g. :meth:`Index.value_counts`)
 - Performance improvement in :meth:`pd.isin` for inputs with more than 1e6 elements (:issue:`36611`)
+- Performance improvement for :meth:`DataFrame.__setitem__` with list-like indexers (:issue:`37954`)
 
 .. ---------------------------------------------------------------------------
 
diff --git a/pandas/core/indexing.py b/pandas/core/indexing.py
index f6cf691ea911c..e7cf8cae28b88 100644
--- a/pandas/core/indexing.py
+++ b/pandas/core/indexing.py
@@ -672,17 +672,12 @@ def _ensure_listlike_indexer(self, key, axis=None, value=None):
             and not com.is_bool_indexer(key)
             and all(is_hashable(k) for k in key)
         ):
-            for i, k in enumerate(key):
-                if k not in self.obj:
-                    if value is None:
-                        self.obj[k] = np.nan
-                    elif is_array_like(value) and value.ndim == 2:
-                        # GH#37964 have to select columnwise in case of array
-                        self.obj[k] = value[:, i]
-                    elif is_list_like(value):
-                        self.obj[k] = value[i]
-                    else:
-                        self.obj[k] = value
+            # GH#38148
+            keys = self.obj.columns.union(key, sort=False)
+
+            self.obj._mgr = self.obj._mgr.reindex_axis(
+                keys, axis=0, copy=False, consolidate=False, only_slice=True
+            )
 
     def __setitem__(self, key, value):
         if isinstance(key, tuple):
diff --git a/pandas/core/internals/managers.py b/pandas/core/internals/managers.py
index 168dba25ba29c..93ab207d8ce12 100644
--- a/pandas/core/internals/managers.py
+++ b/pandas/core/internals/managers.py
@@ -1236,6 +1236,8 @@ def reindex_axis(
         limit=None,
         fill_value=None,
         copy: bool = True,
+        consolidate: bool = True,
+        only_slice: bool = False,
     ):
         """
         Conform block manager to new index.
@@ -1246,7 +1248,13 @@ def reindex_axis(
         )
 
         return self.reindex_indexer(
-            new_index, indexer, axis=axis, fill_value=fill_value, copy=copy
+            new_index,
+            indexer,
+            axis=axis,
+            fill_value=fill_value,
+            copy=copy,
+            consolidate=consolidate,
+            only_slice=only_slice,
         )
 
     def reindex_indexer(
@@ -1258,6 +1266,7 @@ def reindex_indexer(
         allow_dups: bool = False,
         copy: bool = True,
         consolidate: bool = True,
+        only_slice: bool = False,
     ) -> T:
         """
         Parameters
@@ -1270,6 +1279,8 @@ def reindex_indexer(
         copy : bool, default True
         consolidate: bool, default True
             Whether to consolidate inplace before reindexing.
+        only_slice : bool, default False
+            Whether to take views, not copies, along columns.
 
         pandas-indexer with -1's only.
         """
@@ -1293,7 +1304,9 @@ def reindex_indexer(
             raise IndexError("Requested axis not found in manager")
 
         if axis == 0:
-            new_blocks = self._slice_take_blocks_ax0(indexer, fill_value=fill_value)
+            new_blocks = self._slice_take_blocks_ax0(
+                indexer, fill_value=fill_value, only_slice=only_slice
+            )
         else:
             new_blocks = [
                 blk.take_nd(
diff --git a/pandas/tests/frame/indexing/test_setitem.py b/pandas/tests/frame/indexing/test_setitem.py
index e4a66ea9133dd..884cb6c20b77e 100644
--- a/pandas/tests/frame/indexing/test_setitem.py
+++ b/pandas/tests/frame/indexing/test_setitem.py
@@ -319,6 +319,24 @@ def test_setitem_bool_with_numeric_index(self, dtype):
         tm.assert_index_equal(df.columns, expected_cols)
 
 
+class TestDataFrameSetItemWithExpansion:
+    def test_setitem_listlike_views(self):
+        # GH#38148
+        df = DataFrame({"a": [1, 2, 3], "b": [4, 4, 6]})
+
+        # get one column as a view of df
+        ser = df["a"]
+
+        # add columns with list-like indexer
+        df[["c", "d"]] = np.array([[0.1, 0.2], [0.3, 0.4], [0.4, 0.5]])
+
+        # edit in place the first column to check view semantics
+        df.iloc[0, 0] = 100
+
+        expected = Series([100, 2, 3], name="a")
+        tm.assert_series_equal(ser, expected)
+
+
 class TestDataFrameSetItemSlicing:
     def test_setitem_slice_position(self):
         # GH#31469