diff --git a/doc/source/whatsnew/v2.0.0.rst b/doc/source/whatsnew/v2.0.0.rst
index 4577d20a509ce..efb4a572486e3 100644
--- a/doc/source/whatsnew/v2.0.0.rst
+++ b/doc/source/whatsnew/v2.0.0.rst
@@ -629,6 +629,7 @@ Timedelta
 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`)
 -
 
 Numeric
diff --git a/pandas/_libs/tslibs/parsing.pyx b/pandas/_libs/tslibs/parsing.pyx
index 003ce77a221db..232169f3844b3 100644
--- a/pandas/_libs/tslibs/parsing.pyx
+++ b/pandas/_libs/tslibs/parsing.pyx
@@ -894,7 +894,7 @@ def format_is_iso(f: str) -> bint:
 
     for date_sep in [' ', '/', '\\', '-', '.', '']:
         for time_sep in [' ', 'T']:
-            for micro_or_tz in ['', '%z', '%Z', '.%f', '.%f%z', '.%f%Z']:
+            for micro_or_tz in ['', '%z', '.%f', '.%f%z']:
                 if (iso_template(date_sep=date_sep,
                                  time_sep=time_sep,
                                  micro_or_tz=micro_or_tz,
diff --git a/pandas/_libs/tslibs/src/datetime/np_datetime_strings.c b/pandas/_libs/tslibs/src/datetime/np_datetime_strings.c
index 597a2aae7a2a3..7bb94012fad0c 100644
--- a/pandas/_libs/tslibs/src/datetime/np_datetime_strings.c
+++ b/pandas/_libs/tslibs/src/datetime/np_datetime_strings.c
@@ -539,7 +539,7 @@ int parse_iso_8601_datetime(const char *str, int len, int want_exc,
 
     /* UTC specifier */
     if (*substr == 'Z') {
-        if (compare_format(&format, &format_len, "%Z", 2, exact)) {
+        if (compare_format(&format, &format_len, "%z", 2, exact)) {
             goto parse_error;
         }
         /* "Z" should be equivalent to tz offset "+00:00" */
diff --git a/pandas/tests/tools/test_to_datetime.py b/pandas/tests/tools/test_to_datetime.py
index 22dbec337c8b1..4c70aeb3e36aa 100644
--- a/pandas/tests/tools/test_to_datetime.py
+++ b/pandas/tests/tools/test_to_datetime.py
@@ -1755,7 +1755,6 @@ def test_to_datetime_iso8601(self, cache, arg, exp_str):
             ("2012-01-01 10", "%Y-%m-%d %H:%M"),
             ("2012-01-01 10:00", "%Y-%m-%d %H:%M:%S"),
             ("2012-01-01 10:00:00", "%Y-%m-%d %H:%M:%S.%f"),
-            ("2012-01-01 10:00:00.123", "%Y-%m-%d %H:%M:%S.%f%Z"),
             ("2012-01-01 10:00:00.123", "%Y-%m-%d %H:%M:%S.%f%z"),
             (0, "%Y-%m-%d"),
         ],
@@ -1861,7 +1860,7 @@ def test_to_datetime_iso8601_valid(self, input, format):
         [
             ("2020-01-01T00:00:00.000000000+00:00", "%Y-%m-%dT%H:%M:%S.%f%z"),
             ("2020-01-01T00:00:00+00:00", "%Y-%m-%dT%H:%M:%S%z"),
-            ("2020-01-01T00:00:00Z", "%Y-%m-%dT%H:%M:%S%Z"),
+            ("2020-01-01T00:00:00Z", "%Y-%m-%dT%H:%M:%S%z"),
         ],
     )
     def test_to_datetime_iso8601_with_timezone_valid(self, input, format):
@@ -1916,6 +1915,12 @@ def test_to_datetime_with_apply(self, cache):
         result = td.apply(to_datetime, format="%b %y", cache=cache)
         tm.assert_series_equal(result, expected)
 
+    def test_to_datetime_timezone_name(self):
+        # https://github.com/pandas-dev/pandas/issues/49748
+        result = to_datetime("2020-01-01 00:00:00UTC", format="%Y-%m-%d %H:%M:%S%Z")
+        expected = Timestamp(2020, 1, 1).tz_localize("UTC")
+        assert result == expected
+
     @td.skip_if_not_us_locale
     def test_to_datetime_with_apply_with_empty_str(self, cache):
         # this is only locale tested with US/None locales
diff --git a/pandas/tests/tslibs/test_parsing.py b/pandas/tests/tslibs/test_parsing.py
index 629144341f5cb..4d7501cdadcd9 100644
--- a/pandas/tests/tslibs/test_parsing.py
+++ b/pandas/tests/tslibs/test_parsing.py
@@ -284,10 +284,10 @@ def test_parse_time_string_check_instance_type_raise_exception():
         ("%Y%m%d %H:%M:%S", True),
         ("%Y-%m-%dT%H:%M:%S", True),
         ("%Y-%m-%dT%H:%M:%S%z", True),
-        ("%Y-%m-%dT%H:%M:%S%Z", True),
+        ("%Y-%m-%dT%H:%M:%S%Z", False),
         ("%Y-%m-%dT%H:%M:%S.%f", True),
         ("%Y-%m-%dT%H:%M:%S.%f%z", True),
-        ("%Y-%m-%dT%H:%M:%S.%f%Z", True),
+        ("%Y-%m-%dT%H:%M:%S.%f%Z", False),
         ("%Y%m%d", False),
         ("%Y%m", False),
         ("%Y", False),