Best friends and nerds Lewis Skolnick and Gilbert Lowe enroll in Adams College to study computer science. They are kicked out of the freshmen dorms by the Alpha Betas, a fraternity composed primarily of football team members, after the Alphas carelessly burn down their own frat house. Dean Ulich sets up the freshmen in temporary quarters in the school's gymnasium, but allows them to rush the fraternities to alleviate their housing situation. Lewis, Gilbert, and other nerds fail to gain fraternity membership, but are able to rent and completely renovate a rundown two-story campus house.
Their success irks Stan Gable, the lead Alpha Beta and Adams' star quarterback; he sets his fellow fraternity members against the nerds, pulling several pranks. The nerds approach the campus police for help, but are bound by the fraternities' Greek Council that adjudicates all such pranks; the only way to appeal the Greek Council's inaction is to join a national fraternity. The nerds attempt to gain national membership, eventually selecting the black fraternity Lambda Lambda Lambda (Tri-Lambs). The head of the Tri-Lambs, U. N. Jefferson, is not thrilled by the notion of granting a charter to a primarily nerd chapter, but the fraternity's bylaws obligate them to give any chapter applicant a 60-day probationary membership. The nerds invite Jefferson to a Lambda party with the Omega Mu sorority, which contain similar nerdy women including Gilbert's girlfriend Judy; their party is livened up when Booger supplies joints with high quality marijuana. The Alpha Betas, along with the Pi Delta Pis, to which Stan's head cheerleader girlfriend Betty Childs belongs, let a herd of pigs into the party, disrupting it, allowing Jefferson to see the discrimination the nerds face. The nerds later take their revenge on both the Alpha Betas and Pi Delta Pis. Jefferson is impressed by the nerds' willingness to stand up for themselves, and he officially names them a Tri-Lamb chapter.
Despite their fraternity membership, Lewis and Gilbert find their prank charges stonewalled by Stan, who is also president of the Greek Council. The nerds realize they can only stop Stan by the Tri-Lambs winning the upcoming Greek Games during homecoming, becoming the heads of the Greek Council. Using their high intelligence, the nerds, working with the Omega Mus, doggedly stay in second place behind the Alpha Betas and Pi Delta Pis throughout the sporting events. During the costume/charity sale events, the nerds use nude photos of Betty (taken during their earlier revenge pranks) to outsell the Alpha Betas. During this, Lewis, who has fallen in love with Betty, steals Stan's costume and tricks her into having sex with him. Betty is surprised when Lewis reveals his identity, but later admits to Stan that she is in love with a Tri-Lamb.
With the Alpha Betas and nerds in close running, the final event is a musical competition. The nerds readily outdo the Alpha Betas with a techno-computer-driven musical production and win the competition; Lewis quickly nominates Gilbert to become the new president of the Greek Council. Enraged, Coach Harris demands the Alpha Betas take revenge, and Stan, having just learned that Betty has fallen for Lewis, orders the Alpha Betas to trash the nerds' fraternity house.
When the nerds return home and find their house destroyed, Gilbert barges into the pep rally for the football team and tries to demand that he be given the chance to speak. Stan, Coach Harris, and the other Alpha Betas stop him, but Dean Ulich, U. N. Jefferson, and a group of national Tri-Lamb members arrive in force to ensure that Gilbert is allowed to speak. Gilbert speaks out on the discrimination the nerds have endured, causing Lewis to join him and finally to admit his nerd status. Judy and Betty then join their respective boyfriends on stage, and Gilbert asks all alumni who have ever been picked on or made to feel inferior to join them. Most of the audience does so. Dean Ulich then orders the Alpha Betas to repair the nerds' house while allowing the nerds to stay in the Alpha Beta's house until the repairs are completed. When Stan and Ogre protest, Dean Ulich retorts, “You're jocks, go live in the gym”. The nerds and alumni celebrate their victory.
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