I don’t know of any single simple rule. Rather, there are rules for various kinds of cases, purposes, and situations.
This is not so difficult, really; we learn to discriminate among situations and apply the correct rules for all kinds of things. Mastering the comma is much less complicated than, for instance, learning how to cook (which things do you boil, fry, grill, roast, etc., and for how long, and with what preparation and what serving method?), learning the rules and strategies and techniques of some video game, reading music and playing an instrument, writing software code (which does not leave room for approximations and gray areas), and many other things that we tackle in the course of ordinary life. They don’t come naturally; they all take some effort, attention, and practice; and they do, for the most part, make sense.