diff --git a/.github/actions/setup-deps/action.yaml b/.github/actions/setup-deps/action.yaml
index 6af3dd3f9dc..3152caabe76 100644
--- a/.github/actions/setup-deps/action.yaml
+++ b/.github/actions/setup-deps/action.yaml
@@ -33,6 +33,8 @@ inputs:
     default: 'hypothesis'
   matplotlib:
     default: 'matplotlib-base'
+  mda_xdrlib:
+    default: 'mda-xdrlib'
   mmtf-python:
     default: 'mmtf-python'
   networkx:
@@ -111,6 +113,7 @@ runs:
           ${{ inputs.griddataformats }}
           ${{ inputs.hypothesis }}
           ${{ inputs.matplotlib }}
+          ${{ inputs.mda_xdrlib }}
           ${{ inputs.mmtf-python }}
           ${{ inputs.networkx }}
           ${{ inputs.numpy }}
diff --git a/package/CHANGELOG b/package/CHANGELOG
index f201a0045fd..92a5baff309 100644
--- a/package/CHANGELOG
+++ b/package/CHANGELOG
@@ -22,6 +22,9 @@ Fixes
 Enhancements
 
 Changes
+  * The `mda-xdrlib` module is now a core dependency of MDAnalysis
+    replacing the now deprecated `xdrlib` core Python library
+    (PR #4271)
   * ConverterBase class moved from coordinates/base.py to converters/base.py (Issue #3404)
 
 Deprecations
diff --git a/package/MDAnalysis/topology/TPRParser.py b/package/MDAnalysis/topology/TPRParser.py
index 733d8bd994f..6e0093304b7 100644
--- a/package/MDAnalysis/topology/TPRParser.py
+++ b/package/MDAnalysis/topology/TPRParser.py
@@ -158,7 +158,6 @@
 __author__ = "Zhuyi Xue"
 __copyright__ = "GNU Public Licence, v2"
 
-import xdrlib
 
 from . import guessers
 from ..lib.util import openany
diff --git a/package/MDAnalysis/topology/tpr/utils.py b/package/MDAnalysis/topology/tpr/utils.py
index a72fb5dce71..cbe4e47fe8d 100644
--- a/package/MDAnalysis/topology/tpr/utils.py
+++ b/package/MDAnalysis/topology/tpr/utils.py
@@ -48,7 +48,7 @@
 """
 
 import numpy as np
-import xdrlib
+from mda_xdrlib import xdrlib
 import struct
 
 from . import obj
diff --git a/package/pyproject.toml b/package/pyproject.toml
index 6d81f5be713..159f3155397 100644
--- a/package/pyproject.toml
+++ b/package/pyproject.toml
@@ -46,6 +46,7 @@ dependencies = [
     'threadpoolctl',
     'packaging',
     'fasteners',
+    'mda-xdrlib',
 ]
 keywords = [
     "python", "science", "chemistry", "biophysics", "molecular-dynamics",
diff --git a/package/setup.py b/package/setup.py
index 505b55e6546..ff5c864b315 100755
--- a/package/setup.py
+++ b/package/setup.py
@@ -604,6 +604,7 @@ def long_description(readme):
           'threadpoolctl',
           'packaging',
           'fasteners',
+          'mda-xdrlib',
     ]
 
     setup(name='MDAnalysis',