Solution: add `os.environ['QT_MAC_WANTS_LAYER'] = '1'` before invoking the main window. Credit: https://www.loekvandenouweland.com/content/pyside2-big-sur-does-not-show-window.html See https://github.com/calebweinreb/pose_annotator/commit/09d3b69f76be154a59424b9c1b95fb22f4504af4