diff --git a/doc/source/whatsnew/v1.5.3.rst b/doc/source/whatsnew/v1.5.3.rst
index b6c1c857717c7..763f9f87194d5 100644
--- a/doc/source/whatsnew/v1.5.3.rst
+++ b/doc/source/whatsnew/v1.5.3.rst
@@ -33,7 +33,6 @@ Bug fixes
 Other
 ~~~~~
 -
--
 
 .. ---------------------------------------------------------------------------
 .. _whatsnew_153.contributors:
diff --git a/doc/source/whatsnew/v2.0.0.rst b/doc/source/whatsnew/v2.0.0.rst
index 62b0ea5307e41..d0eed405c944c 100644
--- a/doc/source/whatsnew/v2.0.0.rst
+++ b/doc/source/whatsnew/v2.0.0.rst
@@ -671,7 +671,7 @@ Timezones
 ^^^^^^^^^
 - Bug in :meth:`Series.astype` and :meth:`DataFrame.astype` with object-dtype containing multiple timezone-aware ``datetime`` objects with heterogeneous timezones to a :class:`DatetimeTZDtype` incorrectly raising (:issue:`32581`)
 - Bug in :func:`to_datetime` was failing to parse date strings with timezone name when ``format`` was specified with ``%Z`` (:issue:`49748`)
--
+- Better error message when passing invalid values to ``ambiguous`` parameter in :meth:`Timestamp.tz_localize` (:issue:`49565`)
 
 Numeric
 ^^^^^^^
diff --git a/pandas/_libs/tslibs/timestamps.pyx b/pandas/_libs/tslibs/timestamps.pyx
index f987a2feb2717..f25114c273bcf 100644
--- a/pandas/_libs/tslibs/timestamps.pyx
+++ b/pandas/_libs/tslibs/timestamps.pyx
@@ -6,8 +6,8 @@ construction requirements, we need to do object instantiation in python
 (see Timestamp class below). This will serve as a C extension type that
 shadows the python class, where we do any heavy lifting.
 """
-import warnings
 
+import warnings
 cimport cython
 
 import numpy as np
@@ -1946,8 +1946,11 @@ default 'raise'
         >>> pd.NaT.tz_localize()
         NaT
         """
-        if ambiguous == "infer":
-            raise ValueError("Cannot infer offset with only one time.")
+        if not isinstance(ambiguous, bool) and ambiguous not in {"NaT", "raise"}:
+            raise ValueError(
+                        "'ambiguous' parameter must be one of: "
+                        "True, False, 'NaT', 'raise' (default)"
+                    )
 
         nonexistent_options = ("raise", "NaT", "shift_forward", "shift_backward")
         if nonexistent not in nonexistent_options and not PyDelta_Check(nonexistent):
diff --git a/pandas/tests/scalar/timestamp/test_timezones.py b/pandas/tests/scalar/timestamp/test_timezones.py
index 3ebffaad23910..d7db99333cd03 100644
--- a/pandas/tests/scalar/timestamp/test_timezones.py
+++ b/pandas/tests/scalar/timestamp/test_timezones.py
@@ -6,6 +6,7 @@
     datetime,
     timedelta,
 )
+import re
 
 import dateutil
 from dateutil.tz import (
@@ -102,7 +103,10 @@ def test_tz_localize_ambiguous(self):
         ts_no_dst = ts.tz_localize("US/Eastern", ambiguous=False)
 
         assert (ts_no_dst.value - ts_dst.value) / 1e9 == 3600
-        msg = "Cannot infer offset with only one time"
+        msg = re.escape(
+            "'ambiguous' parameter must be one of: "
+            "True, False, 'NaT', 'raise' (default)"
+        )
         with pytest.raises(ValueError, match=msg):
             ts.tz_localize("US/Eastern", ambiguous="infer")
 
@@ -182,8 +186,8 @@ def test_tz_localize_ambiguous_compat(self):
 
         pytz_zone = "Europe/London"
         dateutil_zone = "dateutil/Europe/London"
-        result_pytz = naive.tz_localize(pytz_zone, ambiguous=0)
-        result_dateutil = naive.tz_localize(dateutil_zone, ambiguous=0)
+        result_pytz = naive.tz_localize(pytz_zone, ambiguous=False)
+        result_dateutil = naive.tz_localize(dateutil_zone, ambiguous=False)
         assert result_pytz.value == result_dateutil.value
         assert result_pytz.value == 1382835600000000000
 
@@ -194,8 +198,8 @@ def test_tz_localize_ambiguous_compat(self):
         assert str(result_pytz) == str(result_dateutil)
 
         # 1 hour difference
-        result_pytz = naive.tz_localize(pytz_zone, ambiguous=1)
-        result_dateutil = naive.tz_localize(dateutil_zone, ambiguous=1)
+        result_pytz = naive.tz_localize(pytz_zone, ambiguous=True)
+        result_dateutil = naive.tz_localize(dateutil_zone, ambiguous=True)
         assert result_pytz.value == result_dateutil.value
         assert result_pytz.value == 1382832000000000000
 
@@ -357,7 +361,6 @@ def test_astimezone(self, tzstr):
 
     @td.skip_if_windows
     def test_tz_convert_utc_with_system_utc(self):
-
         # from system utc to real utc
         ts = Timestamp("2001-01-05 11:56", tz=timezones.maybe_get_tz("dateutil/UTC"))
         # check that the time hasn't changed.