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.

Teenager Deacon works at a video shop, and his buddies, Fred and Matt, sell the bootleg porno films he acquires. Deacon gets fired, but the pals have the bright idea of filming their own Internet porn flick in order to make money and become more popular at school. Hijinks ensue as they cast and create their movie, but porn industry player Vic Ramalot grows jealous of their burgeoning success and tries to put a stop to the project.

When geeky Ethan discovers three fellow students scamming the examination system, he blackmails them to win over the college's most popular girl.