Erik Stifler (John White) has a difficult time living up to his family name. He is Steve and Matt Stifler’s cousin. He is perhaps the only Stifler about to graduate from high school as a virgin. The film opens with Erik feigning illness so that he can stay home and masturbate. Unfortunately, just as he is about to ejaculate, his parents and grandmother unexpectedly walk into the door and are hit with Erik’s semen, after which his grandmother dies of a heart attack. Erik’s dad later surmises that, as a Stifler, his son should be out having sex instead of masturbating. Erik’s girlfriend of two years, Tracy (Jessy Schram), loves him, but is not ready for intercourse. Tracy decides to have sex, their first attempt goes horribly wrong, and she backs out of trying again.
Erik’s friends Cooze (Jake Siegel) and Ryan (Ross Thomas) plan a road trip to visit Erik’s cousin Dwight Stifler (Steve Talley) in Michigan during an event known as the Naked Mile. Tracy sees this as an opportunity to give Erik a “guilt free weekend pass,” hoping that he can quench his lust and get sex out of his system since she is not ready.
As soon as Erik and his friends arrive on campus, they witness an over-the-top drinking contest where Dwight is crowned a campus champion. Later, they lose a rough game of football against a bitter rival fraternity composed almost entirely of midgets, and end up in a brawl with those same midgets on several occasions. The first night when the guys are at a college bar, Erik meets a college girl named Brandi (Candace Kroslak) who has a fetish for virgin boys, prompting Ryan and Cooze to make a bet with each other that Erik won’t sleep with Brandi and will remain a virgin. At the same time, Ryan and Cooze end up getting turned down by a couple of girls they have met at the bar, Jill and Alexis, who are taken by a couple of the midgets.
The following morning, Dwight gets jumped by the midget fraternity in disguise while walking down the street, landing him in the hospital. Dwight tells the guys he probably won’t make it to the Naked Mile, but yet still manages to make it right in time. Right away, he joins up with Erik, Ryan, and Cooze, who are at first reluctant to run, but when Brandi, Jill, and Alexis show up to run with the guys, they’re finally prompted to strip down and run with the girls, and end up having a great time. Finally as Erik and Brandi reach the finish line, they steal a kiss, which is then caught on camera for a news report on TV. Watching the news report about the Naked Mile back at home, Tracy is upset and feels guilty that she allowed Erik the free pass. Her friends convince her to also lose her virginity before he gets back.
Later that evening, Erik realizes that he loves Tracy, confesses to Brandi that he can’t sleep with her, and rushes back to see his girlfriend. When he gets to her house, Tracy’s dad says she is at a party and Erik arrives at the party just as Tracy has headed upstairs, presumably to lose her virginity to her ex-boyfriend. Erik loudly pounds on the closed bedroom door, proclaiming his love for her. However, Tracy was not in the room because she had decided that she could not go through with her plans. The two decide that they should be each other’s first, and they make love.