Tracy Turnblad is an overweight high school student living in Baltimore, Maryland ("Good Morning Baltimore"). She and her classmate Penny Pingleton frequently watch the The Corny Collins Show, a local teen dance television show, together ("The Nicest Kids in Town").
The teenagers featured on the show attend Tracy and Penny's school, among them Amber von Tussle and her boyfriend Link Larkin, the lead male dancer. Amber’s mother, Velma, manages WYZT and makes sure Amber is prominently featured. Corny Collins and the dancers on the show are white, and Velma only allows African-American kids on the show once a month on "Negro Day", hosted by R&B disc jockey Motormouth Maybelle.
One day, one of the dancers on the show takes a leave of absence and auditions for a replacement are held. Tracy attends, but is rejected by Velma for being overweight and for supporting integration ("The Legend of Miss Baltimore Crabs"). Tracy is sent to detention for skipping school and discovers the "Negro Day" kids practicing in the detention room. Tracy befriends Seaweed (Elijah Kelley), the students' best dancer and Motormouth Maybelle's son, who teaches Tracy several dance moves. As Tracy leaves detention, she inadvertently bumps into Link and dreams of a life with him ("I Can Hear the Bells"). At a record hop, Tracy’s moves attract the attention of Corny Collins ("Ladies' Choice") and he chooses her to join the show ("The Nicest Kids in Town (Reprise)").
Tracy becomes one of Corny's most popular dancers, threatening Amber's chances of winning the show's yearly "Miss Teenage Hairspray" pageant ("The New Girl in Town") and her relationship with Link, as he grows fonder of Tracy. Mr. Pinky suggests that Tracy be the spokesgirl for his Hefty Hideaway boutique. Tracy persuades her agoraphobic mother, Edna, to accompany her to the boutique as her agent ("Welcome to the '60s").
Tracy introduces Seaweed to Penny, and the two are smitten. Later, when Tracy and Link are in detention, Seaweed invites the girls and Link to follow him and his sister Little Inez (Taylor Parks) to a party at Maybelle's store ("Run and Tell That"). Edna finds Tracy there and tries taking her home, but Maybelle convinces her to stay and tells her to take pride in herself ("Big, Blonde and Beautiful"). At the party, Maybelle informs everyone that Velma has canceled "Negro Day" and Tracy suggests that they march for integration. Edna returns to her husband Wilbur's shop, but Velma gets there first and tries to seduce him ("Big, Blonde and Beautiful (Reprise)"). After accusing Wilbur of infidelity, Edna forbids Tracy to be on the show. Wilbur and Edna reconcile ("(You’re) Timeless to Me").
The next morning, Tracy sneaks out of the house to join the protest ("I Know Where I've Been"), which is halted by a police roadblock. The protesters engage in a brawl, while Tracy runs to the Pingletons' home and hides in a fallout shelter. Penny's mother, Prudence, catches Tracy and calls the police before tying her daughter to her bed. Having been bailed out by Wilbur, Seaweed and his friends help Tracy and Penny escape. Link visits Tracy’s house to look for her and realizes he loves her. Seaweed and Penny also acknowledge their love during the escape ("Without Love").
With the pageant underway ("Hairspray"), Velma places police officers around WYZT to stop Tracy. She also changes the pageant tallies so Amber is guaranteed to win. Penny arrives at the pageant with Edna, while Wilbur, Seaweed, and the Negro Day kids help Tracy infiltrate the studio. Link breaks away from Amber to dance with Tracy; later, he pulls Seaweed's sister, Little Inez, to the stage to dance in the pageant.
Amber's attempt to re-claim her championship crown fails. Little Inez wins the pageant, successfully integrating The Corny Collins Show. Velma confesses her tally-switching scheme to her daughter in front of a camera, resulting in her firing. The Corny Collins Show set turns into a celebration as Tracy and Link kiss ("You Can’t Stop the Beat").