diff --git a/profiles/arch/riscv/use.mask b/profiles/arch/riscv/use.mask
index 702524e3a4790..dfdacea6f24d9 100644
--- a/profiles/arch/riscv/use.mask
+++ b/profiles/arch/riscv/use.mask
@@ -6,9 +6,6 @@
 
 # Unmask systemd
 -systemd
-# Our Python has a lot of trouble with the two-level libdir.
-python_targets_python2_7
-python_single_target_python2_7
 
 # Ben Kohler <bkohler@gentoo.org> (2019-01-09)
 # no fam providers keyworded yet
diff --git a/profiles/base/make.defaults b/profiles/base/make.defaults
index 981eda7446a78..d77cffe03f212 100644
--- a/profiles/base/make.defaults
+++ b/profiles/base/make.defaults
@@ -123,13 +123,13 @@ PYTHONDONTWRITEBYTECODE="1"
 # This MUST be kept in sync with the PYTHON_TARGETS below
 # Mike Gilbert <floppym@gentoo.org> (2018-05-23)
 # sys-apps/baslayout-2.5 needs split-usr enabled.
-BOOTSTRAP_USE="unicode internal-glib pkg-config split-usr python_targets_python3_8 python_targets_python2_7"
+BOOTSTRAP_USE="unicode internal-glib pkg-config split-usr python_targets_python3_8"
 
 # Mike Gilbert <floppym@gentoo.org> (2012-05-15)
 # Default target(s) for python-r1.eclass
 # Mikle Kolyada <zlogene@gentoo.org> (2020-12-02)
 # Updated to python3_8
-PYTHON_TARGETS="python2_7 python3_8"
+PYTHON_TARGETS="python3_8"
 PYTHON_SINGLE_TARGET="python3_8"
 
 # Michał Górny <mgorny@gentoo.org> (2013-08-10)
diff --git a/profiles/base/package.use.force b/profiles/base/package.use.force
index 7fccdd3e1850c..10958c1f917c6 100644
--- a/profiles/base/package.use.force
+++ b/profiles/base/package.use.force
@@ -166,7 +166,6 @@ app-shells/bash:0 readline
 # Michał Górny <mgorny@gentoo.org> (2012-10-14)
 # Force-enable all PYTHON_TARGETS for python-exec to avoid using private
 # API. Please remember to keep it in sync with python_targets.desc.
-dev-lang/python-exec python_targets_python2_7
 dev-lang/python-exec python_targets_python3_7
 dev-lang/python-exec python_targets_python3_8
 dev-lang/python-exec python_targets_python3_9
diff --git a/profiles/desc/python_single_target.desc b/profiles/desc/python_single_target.desc
index 08637d9955cf6..1be4dd4001a62 100644
--- a/profiles/desc/python_single_target.desc
+++ b/profiles/desc/python_single_target.desc
@@ -3,7 +3,6 @@
 
 # This file contains descriptions of PYTHON_SINGLE_TARGET USE_EXPAND flags.
 
-python2_7 - Build for Python 2.7 only
 python3_7 - Build for Python 3.7 only
 python3_8 - Build for Python 3.8 only
 python3_9 - Build for Python 3.9 only
diff --git a/profiles/desc/python_targets.desc b/profiles/desc/python_targets.desc
index 0bea2b637481b..66d152ff98c0f 100644
--- a/profiles/desc/python_targets.desc
+++ b/profiles/desc/python_targets.desc
@@ -3,7 +3,6 @@
 
 # This file contains descriptions of PYTHON_TARGETS USE_EXPAND flags.
 
-python2_7 - Build with Python 2.7
 python3_7 - Build with Python 3.7
 python3_8 - Build with Python 3.8
 python3_9 - Build with Python 3.9
diff --git a/profiles/prefix/make.defaults b/profiles/prefix/make.defaults
index 77e5de4327002..cf9a80a852560 100644
--- a/profiles/prefix/make.defaults
+++ b/profiles/prefix/make.defaults
@@ -7,9 +7,3 @@
 # ncurses:   a nice working console drawing library
 # ssl:       encrypted connections are a nice feature
 USE="readline zlib ncurses ssl"
-
-
-# In Prefix, aim for Python 3 only, leaving out 2 to avoid unnecessary
-# builds
-# NOTE: Both are incremental variables: Need to drop obsolete base values.
-PYTHON_TARGETS="-python2_7"