At a high-school party, four friends find that losing their collective virginity isn't as easy as they had thought. But they still believe that they need to do so before college. To motivate themselves, they enter a pact to all "score" by their senior prom.

Ten years after the first American Pie movie, three new hapless virgins discover the Bible hidden in the school library at East Great Falls High. Unfortunately for them, the book is ruined, and with incomplete advice, the Bible leads them on a hilarious journey to lose their virginity.