diff --git a/.github/workflows/python_wheel_build.yml b/.github/workflows/python_wheel_build.yml
index c32ca8d98cc28..0f55e22bc54a5 100644
--- a/.github/workflows/python_wheel_build.yml
+++ b/.github/workflows/python_wheel_build.yml
@@ -28,7 +28,7 @@ jobs:
     strategy:
       fail-fast: false
       matrix:
-        python: [cp310, cp311, cp312, cp313, cp314]
+        python: [cp311, cp312, cp313, cp314]
         config:
           # `label` is a unique artifact name for each build
           - runner: macos-15
@@ -75,7 +75,7 @@ jobs:
     strategy:
       fail-fast: false
       matrix:
-        python: ["3.10", "3.11", "3.12", "3.13", "3.14"]
+        python: ["3.11", "3.12", "3.13", "3.14"]
         test_config:
           # each runner tests the wheel built on it
           - runner: macos-15
diff --git a/.github/workflows/root-ci.yml b/.github/workflows/root-ci.yml
index 90c7e6664bc00..14b60a49bd153 100644
--- a/.github/workflows/root-ci.yml
+++ b/.github/workflows/root-ci.yml
@@ -402,6 +402,7 @@ jobs:
             overrides: ["CMAKE_BUILD_TYPE=Debug"]
           - image: alma10
           - image: ubuntu22
+            python_venv: "/py-venv-3.12/ROOT-CI"
             overrides: ["imt=Off", "CMAKE_BUILD_TYPE=Debug"]
           - image: ubuntu2404
             overrides: ["CMAKE_BUILD_TYPE=Debug"]
diff --git a/README/ReleaseNotes/v642/index.md b/README/ReleaseNotes/v642/index.md
index b45838cd5bbdb..df0ceee474334 100644
--- a/README/ReleaseNotes/v642/index.md
+++ b/README/ReleaseNotes/v642/index.md
@@ -105,6 +105,8 @@ Note: if you build ROOT with option `dev=ON`, the header `RConfigure.h` will alr
 
 ## Python Interface
 
+ROOT dropped support for Python 3.10, meaning ROOT now requires at least Python 3.11.
+
 ### Connecting Python callables to signals
 
 `TQObject::Connect()` now directly accepts a Python callable as the slot, for
diff --git a/bindings/pyroot/pythonizations/CMakeLists.txt b/bindings/pyroot/pythonizations/CMakeLists.txt
index 04aeb31ac581a..6a72b45733e55 100644
--- a/bindings/pyroot/pythonizations/CMakeLists.txt
+++ b/bindings/pyroot/pythonizations/CMakeLists.txt
@@ -21,16 +21,12 @@ set(libname ROOTPythonizations)
 
 add_library(${libname} SHARED ${cpp_sources})
 
-# Use what is in the limited API since Python 3.11, if we build with a lower
-# Python version, we don't bother using the limited API.
-if (Python3_VERSION VERSION_GREATER_EQUAL "3.11")
-  # On Windows we can't use the stable ABI yet: it requires linking against a
-  # different libpython, so as long as we don't build all translation units in
-  # the ROOT Pythonization library with the stable ABI we should not use it.
-  # Free-threaded (Py_GIL_DISABLED) interpreters don't support the limited API.
-  if(NOT MSVC AND NOT Python3_GIL_DISABLED)
-    target_compile_options(${libname} PRIVATE -DPy_LIMITED_API=0x030B0000)
-  endif()
+# On Windows we can't use the stable ABI yet: it requires linking against a
+# different libpython, so as long as we don't build all translation units in
+# the ROOT Pythonization library with the stable ABI we should not use it.
+# Free-threaded (Py_GIL_DISABLED) interpreters don't support the limited API.
+if(NOT MSVC AND NOT Python3_GIL_DISABLED)
+  target_compile_options(${libname} PRIVATE -DPy_LIMITED_API=0x030B0000)
 endif()
 
 # Set the suffix to '.so' and the prefix to 'lib'
diff --git a/bindings/tpython/CMakeLists.txt b/bindings/tpython/CMakeLists.txt
index 728bb058efe72..ef759e5d064d3 100644
--- a/bindings/tpython/CMakeLists.txt
+++ b/bindings/tpython/CMakeLists.txt
@@ -30,16 +30,12 @@ ROOT_STANDARD_LIBRARY_PACKAGE(ROOTTPython
     Python3::Python
 )
 
-# Use what is in the limited API since Python 3.10, if we build with a lower
-# Python version, we don't bother using the limited API.
-if (Python3_VERSION VERSION_GREATER_EQUAL "3.10")
-  # On Windows we can't use the stable ABI yet: it requires linking against a
-  # different libpython, so as long as we don't build all translation units in
-  # the ROOT Pythonization library with the stable ABI we should not use it.
-  # Free-threaded (Py_GIL_DISABLED) interpreters don't support the limited API.
-  if(NOT MSVC AND NOT Python3_GIL_DISABLED)
-    target_compile_options(ROOTTPython PRIVATE -DPy_LIMITED_API=0x030A0000)
-  endif()
+# On Windows we can't use the stable ABI yet: it requires linking against a
+# different libpython, so as long as we don't build all translation units in
+# the ROOT Pythonization library with the stable ABI we should not use it.
+# Free-threaded (Py_GIL_DISABLED) interpreters don't support the limited API.
+if(NOT MSVC AND NOT Python3_GIL_DISABLED)
+  target_compile_options(ROOTTPython PRIVATE -DPy_LIMITED_API=0x030A0000)
 endif()
 
 if(MSVC)
diff --git a/cmake/modules/SearchInstalledSoftware.cmake b/cmake/modules/SearchInstalledSoftware.cmake
index 71b257e95ea7e..0787c3c68edac 100644
--- a/cmake/modules/SearchInstalledSoftware.cmake
+++ b/cmake/modules/SearchInstalledSoftware.cmake
@@ -481,7 +481,7 @@ endif()
 if(tmva-pymva)
   list(APPEND python_components NumPy)
 endif()
-find_package(Python3 3.10 COMPONENTS ${python_components})
+find_package(Python3 3.11 COMPONENTS ${python_components})
 
 # Detect whether the found Python interpreter is a free-threaded build
 # (Py_GIL_DISABLED is defined in pyconfig.h). The limited C API is not