In 1962 at the fictional Faber College, two freshmen, Larry "Pinto" Kroger and Kent "Flounder" Dorfman, struggle to fit in. After being rejected by the prestigious Omega Theta Pi house, they stumble upon the Delta Tau Chi fraternity—a haven for misfits and outcasts. The Delta brothers, led by the charismatic John "Bluto" Blutarsky, live a carefree and rebellious lifestyle, clashing with the college administration. The Dean of the college, Vernon Wormer, is set on revoking Delta's charter due to their continuous academic shortcomings and wild behavior. Meanwhile, the Deltas engage in various misadventures, from wild parties to a road trip, fostering a bond of brotherhood and an ethos of anti-establishment.

Delta's ongoing rivalry with the Omegas and the college administration escalates, leading to a series of pranks and retaliation. The feud catches the attention of the college's stern and manipulative Dean Wormer, who colludes with the Omega president to find grounds for expelling the Delta members. As tensions rise, the Deltas' unruly actions also affect their love lives, intertwining with the Omegas and further complicating the conflict. A crucial homecoming parade provides the backdrop for the climax of this battle as the Deltas devise a plan to strike back against the Dean and their elitist counterparts.