diff --git a/docs/setup/windows_build.rst b/docs/setup/windows_build.rst
index af670c65b3e6..4899755bf57b 100644
--- a/docs/setup/windows_build.rst
+++ b/docs/setup/windows_build.rst
@@ -78,6 +78,13 @@ the interactive setup process.
     cd mozilla-source
     wget https://hg.mozilla.org/mozilla-central/raw-file/default/python/mozboot/bin/bootstrap.py
     python3 bootstrap.py
+.. note::
+
+    When running ``bootstrap.py`` there will be a UAC prompt (for PowerShell) after
+    selecting the destination directory for the source code clone. This is
+    necessary to add the Microsoft Defender Antivirus exclusions automatically. You
+    should select ``Yes`` on the UAC prompt, otherwise you will need
+    to `follow some manual steps below <https://firefox-source-docs.mozilla.org/setup/windows_build.html#set-antivirus-exclusions>`_.
 
 .. note::
 
@@ -98,22 +105,25 @@ If you aren't modifying the Firefox backend, then select one of the
 :ref:`Artifact Mode <Understanding Artifact Builds>` options. If you are
 building Firefox for Android, you should also see the :ref:`GeckoView Contributor Guide`.
 
-Set antivirus exclusions
-~~~~~~~~~~~~~~~~~~~~~~~~
+Ensure antivirus exclusions
+~~~~~~~~~~~~~~~~~~~~~~~~~~~
 
-Windows Defender and some scanning antivirus products are known to significantly degrade
-build times and sometimes even cause failed builds (due to a "missing file").
-This is usually because we have tests for well-known security bugs that have
-code samples that antivirus software identifies as a threat, automatically
-quarantining/corrupting the files.
+Microsoft Defender Antivirus and some third-party antivirus products
+are known to significantly degrade build times and sometimes even cause failed
+builds (due to a "missing file"). This is usually because we have tests for
+well-known security bugs that have code samples that antivirus software identifies
+as a threat, automatically quarantining/corrupting the files.
 
-To avoid this, add two folders to your antivirus exclusion list:
+To avoid this, add the following folders to your third-party antivirus exclusion list:
 
 -  The ``C:\mozilla-build`` folder.
 -  The directory where the Firefox code is (probably ``C:\mozilla-source``).
+-  The ``%USERPROFILE%/.mozbuild`` directory (probably ``C:\Users\<user>\.mozbuild``).
 
-If you haven't installed an antivirus, then you will need to `add the exclusions
-to Windows Defender
+The ``bootstrap.py`` script attempts to add the above folders to the Microsoft
+Defender Antivirus exclusion list automatically. You should check that they were
+successfully added, but if they're missing you will need to `add the exclusions to
+Microsoft Defender Antivirus manually
 <https://support.microsoft.com/en-ca/help/4028485/windows-10-add-an-exclusion-to-windows-security>`_.
 
 .. note::
diff --git a/python/mozboot/bin/bootstrap.py b/python/mozboot/bin/bootstrap.py
index bd0a28e6fb38..d77e96fa0b1e 100755
--- a/python/mozboot/bin/bootstrap.py
+++ b/python/mozboot/bin/bootstrap.py
@@ -29,6 +29,7 @@ import stat
 import subprocess
 import tempfile
 import zipfile
+import ctypes
 
 from pathlib import Path
 from optparse import OptionParser
@@ -254,7 +255,52 @@ def git_clone_firefox(git: Path, dest: Path, watchman: Path):
             shutil.rmtree(str(tempdir))
 
 
-def clone(vcs, no_interactive):
+def add_microsoft_defender_antivirus_exclusions(dest, no_system_changes):
+    if no_system_changes:
+        return
+
+    powershell_exe = which("powershell")
+
+    if not powershell_exe:
+        return
+
+    def print_attempt_exclusion(path):
+        print(
+            f"Attempting to add exclusion path to Microsoft Defender Antivirus for: {path}"
+        )
+
+    powershell_exe = str(powershell_exe)
+    paths = []
+
+    # mozilla-unified / clone dest
+    repo_dir = Path.cwd() / dest
+    paths.append(repo_dir)
+    print_attempt_exclusion(repo_dir)
+
+    # MOZILLABUILD
+    mozillabuild_dir = os.getenv("MOZILLABUILD")
+    if mozillabuild_dir:
+        paths.append(mozillabuild_dir)
+        print_attempt_exclusion(mozillabuild_dir)
+
+    # .mozbuild
+    mozbuild_dir = Path.home() / ".mozbuild"
+    paths.append(mozbuild_dir)
+    print_attempt_exclusion(mozbuild_dir)
+
+    args = ";".join(f"Add-MpPreference -ExclusionPath '{path}'" for path in paths)
+    command = f'-Command "{args}"'
+
+    # This will attempt to run as administrator by triggering a UAC prompt
+    # for admin credentials. If "No" is selected, no exclusions are added.
+    ctypes.windll.shell32.ShellExecuteW(None, "runas", powershell_exe, command, None, 0)
+
+
+def clone(options):
+    vcs = options.vcs
+    no_interactive = options.no_interactive
+    no_system_changes = options.no_system_changes
+
     hg = which("hg")
     if not hg:
         print(
@@ -289,6 +335,8 @@ def clone(vcs, no_interactive):
     if not dest:
         return None
 
+    add_microsoft_defender_antivirus_exclusions(dest, no_system_changes)
+
     print(f"Cloning Firefox {VCS_HUMAN_READABLE[vcs]} repository to {dest}")
     if vcs == "hg":
         return hg_clone_firefox(binary, dest)
@@ -348,7 +396,7 @@ def main(args):
 
     options, leftover = parser.parse_args(args)
     try:
-        srcdir = clone(options.vcs, options.no_interactive)
+        srcdir = clone(options)
         if not srcdir:
             return 1
         print("Clone complete.")