diff --git a/doc/source/whatsnew/v1.3.0.rst b/doc/source/whatsnew/v1.3.0.rst
index 6a85bfd852e19..bd20144268436 100644
--- a/doc/source/whatsnew/v1.3.0.rst
+++ b/doc/source/whatsnew/v1.3.0.rst
@@ -240,7 +240,7 @@ Timedelta
 
 Timezones
 ^^^^^^^^^
-
+- Bug in different ``tzinfo`` objects representing UTC not being treated as equivalent (:issue:`39216`)
 -
 -
 
diff --git a/pandas/_libs/tslibs/__init__.py b/pandas/_libs/tslibs/__init__.py
index 7723140e3eab1..f08b86aa63574 100644
--- a/pandas/_libs/tslibs/__init__.py
+++ b/pandas/_libs/tslibs/__init__.py
@@ -24,6 +24,7 @@
     "to_offset",
     "Tick",
     "BaseOffset",
+    "tz_compare",
 ]
 
 from . import dtypes
@@ -35,6 +36,7 @@
 from .period import IncompatibleFrequency, Period
 from .timedeltas import Timedelta, delta_to_nanoseconds, ints_to_pytimedelta
 from .timestamps import Timestamp
+from .timezones import tz_compare
 from .tzconversion import tz_convert_from_utc_single
 from .vectorized import (
     dt64arr_to_periodarr,
diff --git a/pandas/_libs/tslibs/timestamps.pyx b/pandas/_libs/tslibs/timestamps.pyx
index df4677a242758..5a1db4eee91be 100644
--- a/pandas/_libs/tslibs/timestamps.pyx
+++ b/pandas/_libs/tslibs/timestamps.pyx
@@ -647,14 +647,12 @@ cdef class _Timestamp(ABCTimestamp):
 
         try:
             stamp += self.strftime('%z')
-            if self.tzinfo:
-                zone = get_timezone(self.tzinfo)
         except ValueError:
             year2000 = self.replace(year=2000)
             stamp += year2000.strftime('%z')
-            if self.tzinfo:
-                zone = get_timezone(self.tzinfo)
 
+        if self.tzinfo:
+            zone = get_timezone(self.tzinfo)
         try:
             stamp += zone.strftime(' %%Z')
         except AttributeError:
diff --git a/pandas/_libs/tslibs/timezones.pyx b/pandas/_libs/tslibs/timezones.pyx
index 3deabc57ec522..0449a8dac51fa 100644
--- a/pandas/_libs/tslibs/timezones.pyx
+++ b/pandas/_libs/tslibs/timezones.pyx
@@ -341,6 +341,12 @@ cpdef bint tz_compare(tzinfo start, tzinfo end):
     bool
     """
     # GH 18523
+    if is_utc(start):
+        # GH#38851 consider pytz/dateutil/stdlib UTCs as equivalent
+        return is_utc(end)
+    elif is_utc(end):
+        # Ensure we don't treat tzlocal as equal to UTC when running in UTC
+        return False
     return get_timezone(start) == get_timezone(end)
 
 
diff --git a/pandas/core/dtypes/cast.py b/pandas/core/dtypes/cast.py
index 0941967ef6bee..6d073a34220f4 100644
--- a/pandas/core/dtypes/cast.py
+++ b/pandas/core/dtypes/cast.py
@@ -35,8 +35,8 @@
     conversion,
     iNaT,
     ints_to_pydatetime,
+    tz_compare,
 )
-from pandas._libs.tslibs.timezones import tz_compare
 from pandas._typing import AnyArrayLike, ArrayLike, Dtype, DtypeObj, Scalar
 from pandas.util._validators import validate_bool_kwarg
 
diff --git a/pandas/core/dtypes/dtypes.py b/pandas/core/dtypes/dtypes.py
index cefab33976ba8..6efcf9e6c8416 100644
--- a/pandas/core/dtypes/dtypes.py
+++ b/pandas/core/dtypes/dtypes.py
@@ -21,8 +21,16 @@
 import pytz
 
 from pandas._libs.interval import Interval
-from pandas._libs.tslibs import NaT, Period, Timestamp, dtypes, timezones, to_offset
-from pandas._libs.tslibs.offsets import BaseOffset
+from pandas._libs.tslibs import (
+    BaseOffset,
+    NaT,
+    Period,
+    Timestamp,
+    dtypes,
+    timezones,
+    to_offset,
+    tz_compare,
+)
 from pandas._typing import Dtype, DtypeObj, Ordered
 
 from pandas.core.dtypes.base import ExtensionDtype, register_extension_dtype
@@ -764,7 +772,7 @@ def __eq__(self, other: Any) -> bool:
         return (
             isinstance(other, DatetimeTZDtype)
             and self.unit == other.unit
-            and str(self.tz) == str(other.tz)
+            and tz_compare(self.tz, other.tz)
         )
 
     def __setstate__(self, state) -> None:
diff --git a/pandas/core/indexes/base.py b/pandas/core/indexes/base.py
index 0b46b43514d92..f44789456eb08 100644
--- a/pandas/core/indexes/base.py
+++ b/pandas/core/indexes/base.py
@@ -28,8 +28,12 @@
 from pandas._libs import algos as libalgos, index as libindex, lib
 import pandas._libs.join as libjoin
 from pandas._libs.lib import is_datetime_array, no_default
-from pandas._libs.tslibs import IncompatibleFrequency, OutOfBoundsDatetime, Timestamp
-from pandas._libs.tslibs.timezones import tz_compare
+from pandas._libs.tslibs import (
+    IncompatibleFrequency,
+    OutOfBoundsDatetime,
+    Timestamp,
+    tz_compare,
+)
 from pandas._typing import AnyArrayLike, ArrayLike, Dtype, DtypeObj, Shape, final
 from pandas.compat.numpy import function as nv
 from pandas.errors import DuplicateLabelError, InvalidIndexError
diff --git a/pandas/tests/dtypes/cast/test_promote.py b/pandas/tests/dtypes/cast/test_promote.py
index 294abafa86812..89b45890458c5 100644
--- a/pandas/tests/dtypes/cast/test_promote.py
+++ b/pandas/tests/dtypes/cast/test_promote.py
@@ -7,7 +7,7 @@
 import numpy as np
 import pytest
 
-from pandas._libs.tslibs import NaT
+from pandas._libs.tslibs import NaT, tz_compare
 
 from pandas.core.dtypes.cast import maybe_promote
 from pandas.core.dtypes.common import (
@@ -431,7 +431,7 @@ def test_maybe_promote_datetimetz_with_datetimetz(tz_aware_fixture, tz_aware_fix
 
     # filling datetimetz with datetimetz casts to object, unless tz matches
     exp_val_for_scalar = fill_value
-    if dtype.tz == fill_dtype.tz:
+    if tz_compare(dtype.tz, fill_dtype.tz):
         expected_dtype = dtype
     else:
         expected_dtype = np.dtype(object)
diff --git a/pandas/tests/series/methods/test_fillna.py b/pandas/tests/series/methods/test_fillna.py
index 69a9a81e66ac4..0bcb37d4880a6 100644
--- a/pandas/tests/series/methods/test_fillna.py
+++ b/pandas/tests/series/methods/test_fillna.py
@@ -727,10 +727,18 @@ def test_fillna_method_and_limit_invalid(self):
 
     def test_fillna_datetime64_with_timezone_tzinfo(self):
         # https://github.com/pandas-dev/pandas/issues/38851
-        s = Series(date_range("2020", periods=3, tz="UTC"))
-        expected = s.astype(object)
-        s[1] = NaT
-        result = s.fillna(datetime(2020, 1, 2, tzinfo=timezone.utc))
+        # different tzinfos representing UTC treated as equal
+        ser = Series(date_range("2020", periods=3, tz="UTC"))
+        expected = ser.copy()
+        ser[1] = NaT
+        result = ser.fillna(datetime(2020, 1, 2, tzinfo=timezone.utc))
+        tm.assert_series_equal(result, expected)
+
+        # but we dont (yet) consider distinct tzinfos for non-UTC tz equivalent
+        ts = Timestamp("2000-01-01", tz="US/Pacific")
+        ser2 = Series(ser._values.tz_convert("dateutil/US/Pacific"))
+        result = ser2.fillna(ts)
+        expected = Series([ser[0], ts, ser[2]], dtype=object)
         tm.assert_series_equal(result, expected)
 
 
diff --git a/pandas/tests/tslibs/test_api.py b/pandas/tests/tslibs/test_api.py
index eca444c9ceb34..4ded555ed8f73 100644
--- a/pandas/tests/tslibs/test_api.py
+++ b/pandas/tests/tslibs/test_api.py
@@ -49,6 +49,7 @@ def test_namespace():
         "localize_pydatetime",
         "tz_convert_from_utc_single",
         "to_offset",
+        "tz_compare",
     ]
 
     expected = set(submodules + api)
diff --git a/pandas/tests/tslibs/test_timezones.py b/pandas/tests/tslibs/test_timezones.py
index e49f511fe3cc4..3e825460d6ddd 100644
--- a/pandas/tests/tslibs/test_timezones.py
+++ b/pandas/tests/tslibs/test_timezones.py
@@ -48,6 +48,14 @@ def test_tzlocal_offset():
     assert ts.value + offset == Timestamp("2011-01-01").value
 
 
+def test_tzlocal_is_not_utc():
+    # even if the machine running the test is localized to UTC
+    tz = dateutil.tz.tzlocal()
+    assert not timezones.is_utc(tz)
+
+    assert not timezones.tz_compare(tz, dateutil.tz.tzutc())
+
+
 @pytest.fixture(
     params=[
         (pytz.timezone("US/Eastern"), lambda tz, x: tz.localize(x)),