diff --git a/LICENSES/SIX b/LICENSES/SIX
deleted file mode 100644
index 6fd669af222d3..0000000000000
--- a/LICENSES/SIX
+++ /dev/null
@@ -1,21 +0,0 @@
-six license (substantial portions used in the python 3 compatibility module)
-===========================================================================
-Copyright (c) 2010-2013 Benjamin Peterson
-
-Permission is hereby granted, free of charge, to any person obtaining a copy
-of this software and associated documentation files (the "Software"), to deal
-in the Software without restriction, including without limitation the rights
-to use, copy, modify, merge, publish, distribute, sublicense, and/or sell
-copies of the Software, and to permit persons to whom the Software is
-furnished to do so, subject to the following conditions:
-#
-The above copyright notice and this permission notice shall be included in all
-copies or substantial portions of the Software.
-#
-THE SOFTWARE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND, EXPRESS OR
-IMPLIED, INCLUDING BUT NOT LIMITED TO THE WARRANTIES OF MERCHANTABILITY,
-FITNESS FOR A PARTICULAR PURPOSE AND NONINFRINGEMENT. IN NO EVENT SHALL THE
-AUTHORS OR COPYRIGHT HOLDERS BE LIABLE FOR ANY CLAIM, DAMAGES OR OTHER
-LIABILITY, WHETHER IN AN ACTION OF CONTRACT, TORT OR OTHERWISE, ARISING FROM,
-OUT OF OR IN CONNECTION WITH THE SOFTWARE OR THE USE OR OTHER DEALINGS IN THE
-SOFTWARE.
diff --git a/pandas/_libs/tslibs/period.pyx b/pandas/_libs/tslibs/period.pyx
index e5b50ae3c19de..624cad2bfa95a 100644
--- a/pandas/_libs/tslibs/period.pyx
+++ b/pandas/_libs/tslibs/period.pyx
@@ -2224,10 +2224,7 @@ cdef class _Period(object):
 
     def __unicode__(self):
         """
-        Return a string representation for a particular DataFrame
-
-        Invoked by unicode(df) in py2 only. Yields a Unicode String in both
-        py2/py3.
+        Return a unicode string representation for a particular DataFrame
         """
         base, mult = get_freq_code(self.freq)
         formatted = period_format(self.ordinal, base)
diff --git a/pandas/_libs/tslibs/strptime.pyx b/pandas/_libs/tslibs/strptime.pyx
index ff9e92aa05bb6..ddd5d0d224264 100644
--- a/pandas/_libs/tslibs/strptime.pyx
+++ b/pandas/_libs/tslibs/strptime.pyx
@@ -7,19 +7,7 @@ import calendar
 import re
 from datetime import date as datetime_date
 
-
-# Python 2 vs Python 3
-try:
-    from thread import allocate_lock as _thread_allocate_lock
-except:
-    try:
-        from _thread import allocate_lock as _thread_allocate_lock
-    except:
-        try:
-            from dummy_thread import allocate_lock as _thread_allocate_lock
-        except:
-            from _dummy_thread import allocate_lock as _thread_allocate_lock
-
+from _thread import allocate_lock as _thread_allocate_lock
 
 import pytz
 
diff --git a/pandas/core/base.py b/pandas/core/base.py
index d4294e59cc845..6842a632223ed 100644
--- a/pandas/core/base.py
+++ b/pandas/core/base.py
@@ -699,12 +699,7 @@ def item(self):
         """
         Return the first element of the underlying data as a python scalar.
         """
-        try:
-            return self.values.item()
-        except IndexError:
-            # copy numpy's message here because Py26 raises an IndexError
-            raise ValueError('can only convert an array of size 1 to a '
-                             'Python scalar')
+        return self.values.item()
 
     @property
     def data(self):
diff --git a/pandas/core/dtypes/cast.py b/pandas/core/dtypes/cast.py
index 78754b13e1705..a2509226bcd8e 100644
--- a/pandas/core/dtypes/cast.py
+++ b/pandas/core/dtypes/cast.py
@@ -636,7 +636,6 @@ def astype_nansafe(arr, dtype, copy=True, skipna=False):
         dtype = pandas_dtype(dtype)
 
     if issubclass(dtype.type, str):
-        # in Py3 that's str, in Py2 that's unicode
         return lib.astype_unicode(arr.ravel(),
                                   skipna=skipna).reshape(arr.shape)
 
diff --git a/pandas/core/frame.py b/pandas/core/frame.py
index fdc99e957e257..98b0555d3d771 100644
--- a/pandas/core/frame.py
+++ b/pandas/core/frame.py
@@ -615,10 +615,7 @@ def _info_repr(self):
 
     def __unicode__(self):
         """
-        Return a string representation for a particular DataFrame.
-
-        Invoked by unicode(df) in py2 only. Yields a Unicode String in both
-        py2/py3.
+        Return a unicode string representation for a particular DataFrame.
         """
         buf = StringIO("")
         if self._info_repr():
@@ -904,16 +901,10 @@ def itertuples(self, index=True, name="Pandas"):
         # use integer indexing because of possible duplicate column names
         arrays.extend(self.iloc[:, k] for k in range(len(self.columns)))
 
-        # Python 3 supports at most 255 arguments to constructor, and
-        # things get slow with this many fields in Python 2
+        # Python 3 supports at most 255 arguments to constructor
         if name is not None and len(self.columns) + index < 256:
-            # `rename` is unsupported in Python 2.6
-            try:
-                itertuple = collections.namedtuple(name, fields, rename=True)
-                return map(itertuple._make, zip(*arrays))
-
-            except Exception:
-                pass
+            itertuple = collections.namedtuple(name, fields, rename=True)
+            return map(itertuple._make, zip(*arrays))
 
         # fallback to regular tuples
         return zip(*arrays)
diff --git a/pandas/core/generic.py b/pandas/core/generic.py
index 885c499c58dfa..f785988d558da 100644
--- a/pandas/core/generic.py
+++ b/pandas/core/generic.py
@@ -2581,11 +2581,8 @@ def to_pickle(self, path, compression='infer',
         protocol : int
             Int which indicates which protocol should be used by the pickler,
             default HIGHEST_PROTOCOL (see [1]_ paragraph 12.1.2). The possible
-            values for this parameter depend on the version of Python. For
-            Python 2.x, possible values are 0, 1, 2. For Python>=3.0, 3 is a
-            valid value. For Python >= 3.4, 4 is a valid value. A negative
-            value for the protocol parameter is equivalent to setting its value
-            to HIGHEST_PROTOCOL.
+            values are 0, 1, 2, 3, 4. A negative value for the protocol
+            parameter is equivalent to setting its value to HIGHEST_PROTOCOL.
 
             .. [1] https://docs.python.org/3/library/pickle.html
             .. versionadded:: 0.21.0
@@ -2838,7 +2835,7 @@ def to_latex(self, buf=None, columns=None, col_space=None, header=True,
             characters in column names.
         encoding : str, optional
             A string representing the encoding to use in the output file,
-            defaults to 'ascii' on Python 2 and 'utf-8' on Python 3.
+            defaults to 'utf-8'.
         decimal : str, default '.'
             Character recognized as decimal separator, e.g. ',' in Europe.
 
@@ -2967,7 +2964,7 @@ def to_csv(self, path_or_buf=None, sep=",", na_rep='', float_format=None,
             Python write mode, default 'w'.
         encoding : str, optional
             A string representing the encoding to use in the output file,
-            defaults to 'ascii' on Python 2 and 'utf-8' on Python 3.
+            defaults to 'utf-8'.
         compression : str, default 'infer'
             Compression mode among the following possible values: {'infer',
             'gzip', 'bz2', 'zip', 'xz', None}. If 'infer' and `path_or_buf`
diff --git a/pandas/core/indexes/base.py b/pandas/core/indexes/base.py
index 98647a6895574..b89dc4c769c26 100644
--- a/pandas/core/indexes/base.py
+++ b/pandas/core/indexes/base.py
@@ -921,10 +921,7 @@ def __deepcopy__(self, memo=None):
 
     def __unicode__(self):
         """
-        Return a string representation for this object.
-
-        Invoked by unicode(df) in py2 only. Yields a Unicode String in both
-        py2/py3.
+        Return a unicode string representation for this object.
         """
         klass = self.__class__.__name__
         data = self._format_data()
diff --git a/pandas/core/indexes/frozen.py b/pandas/core/indexes/frozen.py
index 982645ebd5124..cad094e59b022 100644
--- a/pandas/core/indexes/frozen.py
+++ b/pandas/core/indexes/frozen.py
@@ -151,10 +151,7 @@ def values(self):
 
     def __unicode__(self):
         """
-        Return a string representation for this object.
-
-        Invoked by unicode(df) in py2 only. Yields a Unicode String in both
-        py2/py3.
+        Return a unicode string representation for this object.
         """
         prepr = pprint_thing(self, escape_chars=('\t', '\r', '\n'),
                              quote_strings=True)
diff --git a/pandas/core/indexes/range.py b/pandas/core/indexes/range.py
index da6a917c93ba4..5832d106dae34 100644
--- a/pandas/core/indexes/range.py
+++ b/pandas/core/indexes/range.py
@@ -126,7 +126,7 @@ def ensure_int(value, field):
 
     @classmethod
     def from_range(cls, data, name=None, dtype=None, **kwargs):
-        """ Create RangeIndex from a range (py3), or xrange (py2) object. """
+        """ Create RangeIndex from a range object. """
         if not isinstance(data, range):
             raise TypeError(
                 '{0}(...) must be called with object coercible to a '
diff --git a/pandas/core/panel.py b/pandas/core/panel.py
index 542b1075313bf..4181f6c8ca3ab 100644
--- a/pandas/core/panel.py
+++ b/pandas/core/panel.py
@@ -345,10 +345,7 @@ def _compare_constructor(self, other, func):
 
     def __unicode__(self):
         """
-        Return a string representation for a particular Panel.
-
-        Invoked by unicode(df) in py2 only.
-        Yields a Unicode String in both py2/py3.
+        Return a unicode string representation for a particular Panel.
         """
 
         class_name = str(self.__class__)
diff --git a/pandas/core/series.py b/pandas/core/series.py
index 8a22765d85aec..65050db8c4380 100644
--- a/pandas/core/series.py
+++ b/pandas/core/series.py
@@ -1374,10 +1374,7 @@ def reset_index(self, level=None, drop=False, name=None, inplace=False):
 
     def __unicode__(self):
         """
-        Return a string representation for a particular DataFrame.
-
-        Invoked by unicode(df) in py2 only. Yields a Unicode String in both
-        py2/py3.
+        Return a unicode string representation for a particular DataFrame.
         """
         buf = StringIO("")
         width, height = get_terminal_size()
diff --git a/pandas/io/clipboard/clipboards.py b/pandas/io/clipboard/clipboards.py
index b7bed084d72f1..3c8abe74912fd 100644
--- a/pandas/io/clipboard/clipboards.py
+++ b/pandas/io/clipboard/clipboards.py
@@ -33,11 +33,7 @@ def copy_gtk(text):
 
     def paste_gtk():
         clipboardContents = gtk.Clipboard().wait_for_text()
-        # for python 2, returns None if the clipboard is blank.
-        if clipboardContents is None:
-            return ''
-        else:
-            return clipboardContents
+        return clipboardContents
 
     return copy_gtk, paste_gtk
 
diff --git a/pandas/io/formats/printing.py b/pandas/io/formats/printing.py
index 0e6366705c98a..bee66fcbfaa82 100644
--- a/pandas/io/formats/printing.py
+++ b/pandas/io/formats/printing.py
@@ -175,7 +175,7 @@ def pprint_thing(thing, _nest_lvl=0, escape_chars=None, default_escapes=False,
 
     Returns
     -------
-    result - unicode object on py2, str on py3. Always Unicode.
+    result - unicode str
 
     """
 
diff --git a/pandas/io/parsers.py b/pandas/io/parsers.py
index 5d73b377838b6..56ba842fa26a2 100755
--- a/pandas/io/parsers.py
+++ b/pandas/io/parsers.py
@@ -1326,12 +1326,6 @@ def _validate_usecols_arg(usecols):
 
         usecols = set(usecols)
 
-        if usecols_dtype == "unicode":
-            # see gh-13253
-            #
-            # Python 2.x compatibility
-            usecols = {col.encode("utf-8") for col in usecols}
-
         return usecols, usecols_dtype
     return usecols, None
 
diff --git a/pandas/tests/extension/json/array.py b/pandas/tests/extension/json/array.py
index 45574262354f5..4b93f0e12e32a 100644
--- a/pandas/tests/extension/json/array.py
+++ b/pandas/tests/extension/json/array.py
@@ -27,12 +27,7 @@
 class JSONDtype(ExtensionDtype):
     type = abc.Mapping
     name = 'json'
-
-    try:
-        na_value = UserDict()
-    except AttributeError:
-        # source compatibility with Py2.
-        na_value = {}
+    na_value = UserDict()
 
     @classmethod
     def construct_array_type(cls):
diff --git a/pandas/tests/extension/test_integer.py b/pandas/tests/extension/test_integer.py
index a8dcabbb824d5..e9f96390821a6 100644
--- a/pandas/tests/extension/test_integer.py
+++ b/pandas/tests/extension/test_integer.py
@@ -113,10 +113,7 @@ def _check_op(self, s, op, other, op_name, exc=NotImplementedError):
             result = op(s, other)
             expected = s.combine(other, op)
 
-            if op_name == '__rdiv__':
-                # combine is not giving the correct result for this case
-                pytest.skip("skipping reverse div in python 2")
-            elif op_name in ('__rtruediv__', '__truediv__', '__div__'):
+            if op_name in ('__rtruediv__', '__truediv__', '__div__'):
                 expected = expected.astype(float)
                 if op_name == '__rtruediv__':
                     # TODO reverse operators result in object dtype
diff --git a/pandas/tests/indexes/test_base.py b/pandas/tests/indexes/test_base.py
index 116a12c1c520b..2a9246a5a9554 100644
--- a/pandas/tests/indexes/test_base.py
+++ b/pandas/tests/indexes/test_base.py
@@ -6,7 +6,6 @@
 import math
 import operator
 import re
-import sys
 
 import numpy as np
 import pytest
@@ -414,9 +413,6 @@ def test_constructor_dtypes_datetime(self, tz_naive_fixture, attr, utc,
         index = index.tz_localize(tz_naive_fixture)
         dtype = index.dtype
 
-        # TODO(GH-24559): Remove the sys.modules and warnings
-        # not sure what this is from. It's Py2 only.
-        modules = [sys.modules['pandas.core.indexes.base']]
         if (tz_naive_fixture and attr == "asi8" and
                 str(tz_naive_fixture) not in ('UTC', 'tzutc()', 'UTC+00:00')):
             ex_warn = FutureWarning
@@ -425,8 +421,7 @@ def test_constructor_dtypes_datetime(self, tz_naive_fixture, attr, utc,
 
         # stacklevel is checked elsewhere. We don't do it here since
         # Index will have an frame, throwing off the expected.
-        with tm.assert_produces_warning(ex_warn, check_stacklevel=False,
-                                        clear=modules):
+        with tm.assert_produces_warning(ex_warn, check_stacklevel=False):
             result = klass(arg, tz=tz_naive_fixture)
         tm.assert_index_equal(result, index)
 
diff --git a/pandas/tests/io/formats/test_to_csv.py b/pandas/tests/io/formats/test_to_csv.py
index fbd71dfa8262b..c0b41691a67ef 100644
--- a/pandas/tests/io/formats/test_to_csv.py
+++ b/pandas/tests/io/formats/test_to_csv.py
@@ -49,8 +49,7 @@ def test_to_csv_defualt_encoding(self):
         df = DataFrame({'col': ["AAAAA", "ÄÄÄÄÄ", "ßßßßß", "聞聞聞聞聞"]})
 
         with tm.ensure_clean('test.csv') as path:
-            # the default to_csv encoding in Python 2 is ascii, and that in
-            # Python 3 is uft-8.
+            # the default to_csv encoding is uft-8.
             df.to_csv(path)
             tm.assert_frame_equal(pd.read_csv(path, index_col=0), df)
 
diff --git a/pandas/tests/io/parser/test_c_parser_only.py b/pandas/tests/io/parser/test_c_parser_only.py
index 22157a742bacc..0b5fe1623699c 100644
--- a/pandas/tests/io/parser/test_c_parser_only.py
+++ b/pandas/tests/io/parser/test_c_parser_only.py
@@ -416,7 +416,7 @@ def test_read_nrows_large(c_parser_only):
 
 
 def test_float_precision_round_trip_with_text(c_parser_only):
-    # see gh-15140 - This should not segfault on Python 2.7+
+    # see gh-15140
     parser = c_parser_only
     df = parser.read_csv(StringIO("a"), header=None,
                          float_precision="round_trip")
diff --git a/pandas/tests/io/test_compression.py b/pandas/tests/io/test_compression.py
index a3fb35f9f01f2..c0e19f07c148d 100644
--- a/pandas/tests/io/test_compression.py
+++ b/pandas/tests/io/test_compression.py
@@ -100,11 +100,6 @@ def test_series_compression_defaults_to_infer(
 def test_compression_warning(compression_only):
     # Assert that passing a file object to to_csv while explicitly specifying a
     # compression protocol triggers a RuntimeWarning, as per GH21227.
-    # Note that pytest has an issue that causes assert_produces_warning to fail
-    # in Python 2 if the warning has occurred in previous tests
-    # (see https://git.io/fNEBm & https://git.io/fNEBC). Hence, should this
-    # test fail in just Python 2 builds, it likely indicates that other tests
-    # are producing RuntimeWarnings, thereby triggering the pytest bug.
     df = pd.DataFrame(100 * [[0.123456, 0.234567, 0.567567],
                              [12.32112, 123123.2, 321321.2]],
                       columns=['X', 'Y', 'Z'])
diff --git a/pandas/tests/io/test_pickle.py b/pandas/tests/io/test_pickle.py
index b4e942fc086a9..872267e86d95f 100644
--- a/pandas/tests/io/test_pickle.py
+++ b/pandas/tests/io/test_pickle.py
@@ -67,15 +67,7 @@ def compare_element(result, expected, typ, version=None):
 
 def compare(data, vf, version):
 
-    # py3 compat when reading py2 pickle
-    try:
-        data = pd.read_pickle(vf)
-    except (ValueError) as e:
-        if 'unsupported pickle protocol:' in str(e):
-            # trying to read a py3 pickle in py2
-            return
-        else:
-            raise
+    data = pd.read_pickle(vf)
 
     m = globals()
     for typ, dv in data.items():
diff --git a/scripts/merge-pr.py b/scripts/merge-pr.py
index b9233abe56149..5c665faac5976 100755
--- a/scripts/merge-pr.py
+++ b/scripts/merge-pr.py
@@ -30,8 +30,6 @@
 import sys
 import textwrap
 
-from six.moves import input
-
 PANDAS_HOME = '.'
 PROJECT_NAME = 'pandas'
 print("PANDAS_HOME = " + PANDAS_HOME)