diff --git a/doc/source/whatsnew/v3.0.0.rst b/doc/source/whatsnew/v3.0.0.rst
index 4a6cf117fd196..f7b49b81d767c 100644
--- a/doc/source/whatsnew/v3.0.0.rst
+++ b/doc/source/whatsnew/v3.0.0.rst
@@ -694,6 +694,7 @@ Interval
 Indexing
 ^^^^^^^^
 - Bug in :meth:`DataFrame.__getitem__` returning modified columns when called with ``slice`` in Python 3.12 (:issue:`57500`)
+- Bug in :meth:`DataFrame.__setitem__` throwing a ``ValueError`` when setting a column with a 2D object array (:issue:`61026`)
 - Bug in :meth:`DataFrame.from_records` throwing a ``ValueError`` when passed an empty list in ``index`` (:issue:`58594`)
 - Bug in :meth:`DataFrame.loc` with inconsistent behavior of loc-set with 2 given indexes to Series (:issue:`59933`)
 - Bug in :meth:`MultiIndex.insert` when a new value inserted to a datetime-like level gets cast to ``NaT`` and fails indexing (:issue:`60388`)
diff --git a/pandas/core/construction.py b/pandas/core/construction.py
index ada492787a179..23b292c34eca4 100644
--- a/pandas/core/construction.py
+++ b/pandas/core/construction.py
@@ -612,7 +612,12 @@ def sanitize_array(
         if dtype is None:
             subarr = data
             if data.dtype == object and infer_object:
-                subarr = maybe_infer_to_datetimelike(data)
+                if data.ndim != 1:
+                    # GH#61026
+                    subarr = data.ravel()
+                    if copy:
+                        subarr = subarr.copy()
+                subarr = maybe_infer_to_datetimelike(subarr)
             elif data.dtype.kind == "U" and using_string_dtype():
                 from pandas.core.arrays.string_ import StringDtype
 
diff --git a/pandas/tests/frame/indexing/test_setitem.py b/pandas/tests/frame/indexing/test_setitem.py
index 20dd7b0c4d3e7..e7e119b8bf32c 100644
--- a/pandas/tests/frame/indexing/test_setitem.py
+++ b/pandas/tests/frame/indexing/test_setitem.py
@@ -816,6 +816,23 @@ def test_setitem_index_object_dtype_not_inferring(self):
         )
         tm.assert_frame_equal(df, expected)
 
+    def test_setitem_2d_object_array(self):
+        # GH#61026
+        df = DataFrame(
+            {
+                "c1": [1, 2, 3, 4, 5],
+            }
+        )
+        arr = np.array([["A"], ["B"], ["C"], ["D"], ["E"]], dtype=object)
+        df["c1"] = arr
+
+        expected = DataFrame(
+            {
+                "c1": ["A", "B", "C", "D", "E"],
+            }
+        )
+        tm.assert_frame_equal(df, expected)
+
 
 class TestSetitemTZAwareValues:
     @pytest.fixture