diff --git a/doc/source/whatsnew/v3.0.0.rst b/doc/source/whatsnew/v3.0.0.rst
index 38755aef32b85..a956e8fe6b30f 100644
--- a/doc/source/whatsnew/v3.0.0.rst
+++ b/doc/source/whatsnew/v3.0.0.rst
@@ -1267,6 +1267,7 @@ Other
 - Bug in printing a :class:`DataFrame` with a :class:`DataFrame` stored in :attr:`DataFrame.attrs` raised a ``ValueError`` (:issue:`60455`)
 - Bug in printing a :class:`Series` with a :class:`DataFrame` stored in :attr:`Series.attrs` raised a ``ValueError`` (:issue:`60568`)
 - Deprecated the keyword ``check_datetimelike_compat`` in :meth:`testing.assert_frame_equal` and :meth:`testing.assert_series_equal` (:issue:`55638`)
+- Fixed bug in :meth:`DataFrame.combine` with non-unique columns (:issue:`51340`)
 - Fixed bug in :meth:`Series.replace` and :meth:`DataFrame.replace` when trying to replace :class:`NA` values in a :class:`Float64Dtype` object with ``np.nan``; this now works with ``pd.set_option("mode.nan_is_na", False)`` and is irrelevant otherwise (:issue:`55127`)
 - Fixed bug in :meth:`Series.replace` and :meth:`DataFrame.replace` when trying to replace :class:`np.nan` values in a :class:`Int64Dtype` object with :class:`NA`; this is now a no-op with ``pd.set_option("mode.nan_is_na", False)`` and is irrelevant otherwise (:issue:`51237`)
 - Fixed bug in the :meth:`Series.rank` with object dtype and extremely small float values (:issue:`62036`)
diff --git a/pandas/core/frame.py b/pandas/core/frame.py
index 68ea6795d47dd..fcd4d6aaf1195 100644
--- a/pandas/core/frame.py
+++ b/pandas/core/frame.py
@@ -194,7 +194,9 @@
     nargsort,
 )
 
-from pandas.io.common import get_handle
+from pandas.io.common import (
+    get_handle,
+)
 from pandas.io.formats import (
     console,
     format as fmt,
@@ -9093,7 +9095,7 @@ def combine(
         2  NaN  3.0 1.0
         """
         other_idxlen = len(other.index)  # save for compare
-        other_columns = other.columns
+        self_columns, other_columns = self.columns, other.columns
 
         this, other = self.align(other)
         new_index = this.index
@@ -9105,12 +9107,12 @@ def combine(
             return other.copy()
 
         # preserve column order
-        new_columns = self.columns.union(other_columns, sort=False)
+        new_columns = self_columns.union(other_columns, sort=False)
         do_fill = fill_value is not None
         result = {}
-        for col in new_columns:
-            series = this[col]
-            other_series = other[col]
+        for i in range(this.shape[1]):
+            series = this.iloc[:, i]
+            other_series = other.iloc[:, i]
 
             this_dtype = series.dtype
             other_dtype = other_series.dtype
@@ -9121,7 +9123,7 @@ def combine(
             # don't overwrite columns unnecessarily
             # DO propagate if this column is not in the intersection
             if not overwrite and other_mask.all():
-                result[col] = this[col].copy()
+                result[this.columns[i]] = this.iloc[:, i].copy()
                 continue
 
             if do_fill:
@@ -9130,7 +9132,7 @@ def combine(
                 series[this_mask] = fill_value
                 other_series[other_mask] = fill_value
 
-            if col not in self.columns:
+            if other.columns[i] not in self.columns:
                 # If self DataFrame does not have col in other DataFrame,
                 # try to promote series, which is all NaN, as other_dtype.
                 new_dtype = other_dtype
@@ -9155,7 +9157,7 @@ def combine(
                     arr, new_dtype
                 )
 
-            result[col] = arr
+            result[this.columns[i]] = arr
 
         # convert_objects just in case
         frame_result = self._constructor(result, index=new_index, columns=new_columns)
diff --git a/pandas/tests/frame/methods/test_combine.py b/pandas/tests/frame/methods/test_combine.py
index bc6a67e4e1f32..abc8fda8fb88d 100644
--- a/pandas/tests/frame/methods/test_combine.py
+++ b/pandas/tests/frame/methods/test_combine.py
@@ -45,3 +45,17 @@ def test_combine_generic(self, float_frame):
         )
         tm.assert_frame_equal(chunk, exp)
         tm.assert_frame_equal(chunk2, exp)
+
+    def test_combine_non_unique_columns(self):
+        # GH#51340
+        df = pd.DataFrame({"A": range(5), "B": range(5)})
+        df.columns = ["A", "A"]
+
+        other = df.copy()
+        df.iloc[1, :] = 11
+
+        def combiner(a, b):
+            return b
+
+        result = df.combine(other, combiner)
+        tm.assert_frame_equal(result, other)