I will score the crap outta plexi with just a utility knife and a straight edge. Then break it and it usually comes off pretty clean at the score. If not, get some pliers to direct the stress right at your score mark, and it will snap off.
I do that to get it within 1/4" of the final size I want, then finish with a flush trim router bit and a wood cutout of the size needed. Router works great, but the less material I have to remove with the router, the better (makes a mess).