diff --git a/doc/source/whatsnew/v2.1.2.rst b/doc/source/whatsnew/v2.1.2.rst
index 145c364728b40..b4e903734c2d8 100644
--- a/doc/source/whatsnew/v2.1.2.rst
+++ b/doc/source/whatsnew/v2.1.2.rst
@@ -18,6 +18,7 @@ Fixed regressions
 - Fixed regression in :meth:`DataFrame.sort_index` which was not sorting correctly when the index was a sliced :class:`MultiIndex` (:issue:`55379`)
 - Fixed performance regression with wide DataFrames, typically involving methods where all columns were accessed individually (:issue:`55256`, :issue:`55245`)
 - Fixed regression in :func:`merge_asof` raising ``TypeError`` for ``by`` with datetime and timedelta dtypes (:issue:`55453`)
+- Fixed regression in :meth:`DataFrame.to_sql` not roundtripping datetime columns correctly for sqlite when using ``detect_types`` (:issue:`55554`)
 
 .. ---------------------------------------------------------------------------
 .. _whatsnew_212.bug_fixes:
diff --git a/pandas/io/sql.py b/pandas/io/sql.py
index 6a62568fc4ce7..b4675513a99c2 100644
--- a/pandas/io/sql.py
+++ b/pandas/io/sql.py
@@ -2094,7 +2094,7 @@ def _adapt_time(t) -> str:
         # Python 3.12+ doesn't auto-register adapters for us anymore
 
         adapt_date_iso = lambda val: val.isoformat()
-        adapt_datetime_iso = lambda val: val.isoformat()
+        adapt_datetime_iso = lambda val: val.isoformat(" ")
 
         sqlite3.register_adapter(time, _adapt_time)
 
@@ -2102,11 +2102,9 @@ def _adapt_time(t) -> str:
         sqlite3.register_adapter(datetime, adapt_datetime_iso)
 
         convert_date = lambda val: date.fromisoformat(val.decode())
-        convert_datetime = lambda val: datetime.fromisoformat(val.decode())
-        convert_timestamp = lambda val: datetime.fromtimestamp(int(val))
+        convert_timestamp = lambda val: datetime.fromisoformat(val.decode())
 
         sqlite3.register_converter("date", convert_date)
-        sqlite3.register_converter("datetime", convert_datetime)
         sqlite3.register_converter("timestamp", convert_timestamp)
 
     def sql_schema(self) -> str:
diff --git a/pandas/tests/io/test_sql.py b/pandas/tests/io/test_sql.py
index 63546b44e92be..fc180c377140a 100644
--- a/pandas/tests/io/test_sql.py
+++ b/pandas/tests/io/test_sql.py
@@ -3333,6 +3333,24 @@ def test_roundtripping_datetimes(sqlite_sqlalchemy_memory_engine):
     assert result == "2020-12-31 12:00:00.000000"
 
 
+@pytest.fixture
+def sqlite_builtin_detect_types():
+    with contextlib.closing(
+        sqlite3.connect(":memory:", detect_types=sqlite3.PARSE_DECLTYPES)
+    ) as closing_conn:
+        with closing_conn as conn:
+            yield conn
+
+
+def test_roundtripping_datetimes_detect_types(sqlite_builtin_detect_types):
+    # https://github.com/pandas-dev/pandas/issues/55554
+    conn = sqlite_builtin_detect_types
+    df = DataFrame({"t": [datetime(2020, 12, 31, 12)]}, dtype="datetime64[ns]")
+    df.to_sql("test", conn, if_exists="replace", index=False)
+    result = pd.read_sql("select * from test", conn).iloc[0, 0]
+    assert result == Timestamp("2020-12-31 12:00:00.000000")
+
+
 @pytest.mark.db
 def test_psycopg2_schema_support(postgresql_psycopg2_engine):
     conn = postgresql_psycopg2_engine