As the movie opens, high school senior Ferris Bueller (Matthew Broderick), decides to skip school on a nice spring day by faking an illness to his parents (Lyman Ward and Cindy Pickett), then encourages his girlfriend, Sloane (Mia Sara), and his pessimistic best friend, Cameron (Alan Ruck), to spend the day in Chicago as one of their last flings before they head off to different colleges. Ferris persuades Cameron to let them use his father's prized convertible 1961 Ferrari 250 GT California to drive into the city. The rest of the school and many residents learn of Ferris' exaggerated illness and offer donations to help "Save Ferris". Only two people are not convinced by Ferris's deception: his often sarcastic sister Jeanie (Jennifer Grey), outraged at Ferris's ability to defy authority easily, and the school's Dean of Students, Edward Rooney (Jeffrey Jones), who correctly believes Ferris to be a truant.
Ferris and his friends arrive downtown and leave the Ferrari with two garage attendants, who drive off in it a short time later to take a joyride. Ferris, Sloane and Cameron enjoy many sights of the city, including taking in a game at Wrigley Field, visiting the Sears Tower, the Art Institute of Chicago, the Chicago Mercantile Exchange and taking part in the Von Steuben Day Parade, with Ferris lip-syncing on a float to "Danke Schoen" and The Beatles' version of "Twist and Shout". Ferris even uses his ploys to pretend he is Abe Froman, the Sausage King of Chicago, to dine at an upscale restaurant, Chez Quis, while narrowly avoiding his father, who is on his way to lunch with business associates.
Meanwhile, Mr. Rooney has gone off-campus to try to find Ferris, first at a local hangout, then traveling to Ferris's home. He tries to gain entry, but ends up getting stuck in the mud and losing his shoe in the process, while being chased by the family's dog. Mr. Rooney eventually gains access, but Jeanie comes home, trying to find Ferris, and discovers Mr. Rooney in the kitchen, mistaking him for a burglar. She highkicks him in the face, and runs upstairs to call the police. This forces Rooney to flee the scene, dropping his wallet. When the police show up, they take Jeanie in for prank calling, and while at the police station, she talks to a drug addict (Charlie Sheen), who tells her that she needs to stop worrying so much about Ferris and more about herself. Jeanie becomes increasingly annoyed with the addict, but is found kissing him when her mother arrives to pick her up, upset at having to do so.
At the end of the day, Ferris and his friends retrieve the Ferrari, but discover on the way back that hundreds of miles have been added to the odometer, sending Cameron into a panic attack with Ferris saying to the audience, "This is where Cameron goes berserk." before Cameron emits a scream of terror, fearing his father's reaction. Finally, Cameron goes temporarily catatonic, even trying to drown himself in the neighbor's pool, before Ferris saves him. After calming Cameron down, Ferris comes up with a plan to run the car in reverse while running in place at Cameron's father's hillside garage, hoping to reverse the odometer. When they realize this is not working, Cameron unleashes his pent-up anger against his father, damaging the front of the Ferrari, but comes to realize he is long due to stand up to his father and vows to accept the consequences. Cameron calms down and rests himself against the car, but his previous actions have unbalanced it from the jack it was on, the car hits the floor, races in reverse and crashes through the glass wall, landing in a ravine behind the house. Despite Ferris' offer to take the blame, Cameron still plans to "take it" and admit his actions to his father.
Ferris walks Sloane home, before realizing he must get home within five minutes. He then races through the backyards of his neighborhood to get back home before his parents. Along the way, he has several close encounters with his family members driving home, but his parents do not notice him. When he arrives home, he is unable to find the house key under the doormat and instead finds Mr. Rooney with the key, saying "Looking for this?" Mr. Rooney then explains to Ferris how he has waited for this day and tells him to expect another year of high school. However, Jeanie finds the two, thanks Mr. Rooney for driving Ferris back from the hospital and shows him the wallet that he left behind when he broke in earlier, throwing it into the mud (where Rooney previously lost his shoe). Mr. Rooney gets attacked by the family's dog, leaving Ferris with enough time to get back into bed just before his parents check on him.
As the credits are rolling, Mr. Rooney, in his disheveled state, is invited by a bus driver to hitch a ride back to school on a school bus as it drives students home. Later, at the end of the credits, Ferris emerges from the bathroom, speaking directly to the audience, "You're still here? It's over. Go home. Go!" before he turns around and goes into the bathroom again.