diff --git a/CHANGES.txt b/CHANGES.txt
index 4991408d9..c8116259e 100644
--- a/CHANGES.txt
+++ b/CHANGES.txt
@@ -7,6 +7,10 @@ However contributors are encouraged to add their own entries for their work.
 Note that, baring some major issue building and cutting the release, build
 228 will be the last version supporting Python 2.
 
+Since build 300:
+----------------
+* Shifted work in win32.lib.pywin32_bootstrap to Python's import system from
+  manual path manipulations (@wkschwartz in #1651)
 
 Since build 228:
 ----------------
diff --git a/win32/Lib/pywin32_bootstrap.py b/win32/Lib/pywin32_bootstrap.py
index 434ed598b..686a59a8f 100644
--- a/win32/Lib/pywin32_bootstrap.py
+++ b/win32/Lib/pywin32_bootstrap.py
@@ -6,29 +6,23 @@
 # modules are imported.
 # If Python has `os.add_dll_directory()`, we need to call it with this path.
 # Otherwise, we add this path to PATH.
-import os
-import site
 
-# The directory should be installed under site-packages.
 
-dirname = os.path.dirname
-# This is to get the "...\Lib\site-packages" directory
-# out of this file name: "...\Lib\site-packages\win32\Lib\pywin32_bootstrap.py".
-# It needs to be searched when installed in virtual environments.
-level3_up_dir = dirname(dirname(dirname(__file__)))
-
-site_packages_dirs = getattr(site, "getsitepackages", lambda: [])()
-if level3_up_dir not in site_packages_dirs:
-    site_packages_dirs.insert(0, level3_up_dir)
-
-for site_packages_dir in site_packages_dirs:
-    pywin32_system32 = os.path.join(site_packages_dir, "pywin32_system32")
-    if os.path.isdir(pywin32_system32):
-        if hasattr(os, "add_dll_directory"):
-            os.add_dll_directory(pywin32_system32)
-        # This is to ensure the pywin32 path is in the beginning to find the
-        # pywin32 DLLs first and prevent other PATH entries to shadow them
-        elif not os.environ["PATH"].startswith(pywin32_system32):
-            os.environ["PATH"] = os.environ["PATH"].replace(os.pathsep + pywin32_system32, "")
-            os.environ["PATH"] = pywin32_system32 + os.pathsep + os.environ["PATH"]
-        break
+try:
+    import pywin32_system32
+except ImportError:  # Python ≥3.6: replace ImportError with ModuleNotFoundError
+    pass
+else:
+    import os
+    # We're guaranteed only that __path__: Iterable[str]
+    # https://docs.python.org/3/reference/import.html#__path__
+    for path in pywin32_system32.__path__:
+        if os.path.isdir(path):
+            if hasattr(os, "add_dll_directory"):
+                os.add_dll_directory(path)
+            # This is to ensure the pywin32 path is in the beginning to find the
+            # pywin32 DLLs first and prevent other PATH entries to shadow them
+            elif not os.environ["PATH"].startswith(path):
+                os.environ["PATH"] = os.environ["PATH"].replace(os.pathsep + path, "")
+                os.environ["PATH"] = path + os.pathsep + os.environ["PATH"]
+            break