Popular parody singer "Weird Al" Yankovic is rushed into the hospital emergency room, near death. A doctor tries to revive him but it is no use. Just as the medical staff "call it", Al sits up and says he has more to do with his life. The audience sees the movie rewind back to the beginning.As a child, Al listens to his favorite host "Dr. Demento" on the radio. One day Al is eating a meal with his parents. His father rants about how bad the factory is and tells Al that is his future. Al says he does not want to work there. Al sings "Amazing Grace" with his own lyrics, naming it "Amazing Grapes". His father tells Al to stop that blasphemy.A traveling salesman shows up with an accordion. Al answers the door and the salesman gives the accordion to Al and tells him how perfect it would be for him. Al wants it but his father beats up the man. Al's mom says she will buy it and Al will secretly learn how to play it.As a high school student, Al is invited to a party but says his father won't let him go. His friends tell him to sneak out so he puts a hay boy in his bed and goes to the party. Polka music is being played and the kids love it. Al is asked to play his accordion, though he is reluctant. Al finally agrees and he is really good. The police show up and break up the party, and Al is taken home. His father destroys the accordion.Out on his own, Al auditions for a punk band by playing his accordion. He is immediately rejected.At the apartment he shares with Steve, Jim and Bermuda, Al is asked what he wants to do with his life. He says he wants to write new lyrics for existing songs. His friends ask him to go ahead and show what he can do, but Al is not inspired. While Al is looking in the refrigerator, his friends turn on the radio and "My Sharona" by The Knack is playing. Al notices the bologna is labeled and asks one of his friends if it is his. The friend responds it is "my bologna" and Al is inspired, especially when The Knack's record gets stuck.Al's friends bring recording equipment to a bus station and he records "My Bologna" with his accordion and sound effects provided by his friends. The recording is sent to DJ Captain Buffoon, who plays it and gets lots of great response. Al takes the recording to the Scotti Brothers, who reject the silly concept.Al and his friends go to a biker bar where the crowd hates the band that rejected Al earlier. Al offers to play his accordion. Amazingly, his friends can play the instruments that are already on stage, and Al changes the lyrics of "I Love Rock and Roll" to "I Love Rocky Road". The song is a hit and one of the bikers demands Rocky Road ice cream.It happens that Dr. Demento, in a tux and top hat, is attending and sees a lot of potential in Al. Al is excited to meet the man he has enjoyed for so long on the radio, and he and his friends attend a party at Dr. Demento's house. Also there are Pee-Wee Herman, Tiny Tim, Alice Cooper, Andy Warhol, Salvador Dali, Alice Cooper, Gallagher and other celebrities. Wolfman Jack crashes the party and is nearly escorted out. Al is asked to show his songwriting talent but he is not inspired. Then John Deacon of Queen, who has to explain who he is, asks Al to rewrite "Another One Bites the Dust". Al and the band perform "Another One Rides the Bus", which most of the party guests love (Gallagher is cynical). Wolfman Jack is ejected.Weird Al is a major music star, with his songs all over the music charts and Oprah Winfrey interviewing him on TV. Madonna is one of his fans. Al's father is not. Dr. Demento gets in one of Al's multiple hot tubs, in Al's huge mansion, and starts giving Al career advice. Dr. Demento wants Al to write original songs, but Al doesn't want to. Then Dr. Demento reveals he put LSD in Al's food, and Al has weird visions and hears people talking about various cereal brands.At last, Al writes his first original song, "Eat It", which is a big hit. He says he is through with parodies. The Scotti brothers finally accept him. And his biggest fan is Madonna, who shows up dressed like one of her music video characters and begins a relationship with Al. She claims to be attracted to him but just wants one of his parodies to help her career. She wants Al to write his version of "Like a Virgin".Though warned about Madonna, Al continues his relationship with her. Then Al finds out Michael Jackson has parodied his "Eat It", with the new lyrics "Beat It". Al gets in an argument with the band before a show and, still drinking, storms off and gets in his car and has an accident. He is rushed to the hospital and the movie's first scene is repeated. Al has his inspiration for the Madonna parody, and he performs "Like a Surgeon" dressed like a doctor. He returns to the show despite medical advice and performs with his band but gets arrested for inappropriate behavior.Al has another big fan, drug lord Pablo Escobar. He has Madonna kidnapped and taken to Colombia, intending for Al to play for his 40th birthday. Al flies to Colombia and using a hay boy as a decoy manages to take out Escobar's guards. Al enters Escobar's house and after refusing to play for him, starts a gunfight. Al appears to be dead but the bullet was stopped by the platinum records he wears on his chest. Al kills Escobar and goes home, dropping Madonna.Al is shown learning a new job at his father's factory. His father is pleased Al wants to work there but he is finally ready to explain why he didn't want his son playing the accordion. Back at home, the father shows Al his art work. The audience sees it turn into animation. Al's father explains he was Amish and music such as polka was seen as evil. Al's father wanted to be an artist and a musician, and he performed accordion music on the street, but he was thrown out of his community. And he didn't want that life for his son. Al's parents want him to continue his career, but he is not feeling inspired. His mother has put on weight, saying, "You know I'm fat, you know it." Also part of the father's collection are the lyrics to an original song, "Amish Paradise".Al rejoins his band and performs his father's song. Coolio is in the audience and it's not clear whether he is annoyed or inspired.At an awards show Al wins a very specific award and is then shot by Madonna. The credits roll. Later, Madonna is grabbed by a hand reaching out from Al's grave.