The McCallister family prepares to spend Christmas in Paris, gathering at Kate and Peter's home in a Chicago suburb on the night before their departure. Kate and Peter's youngest son Kevin is ridiculed by his siblings and cousins due to his immaturity. Kevin inadvertently ruins the family dinner after a scuffle with his oldest brother Buzz, resulting in Kate sending him up to the attic. Frustrated with Kate for allowing the rest of the family to pick on him, Kevin wishes that his family would disappear. During the night, heavy winds create a power outage, disabling the alarm clocks and causing the family to oversleep. In the confusion and rush to get to the airport, Kevin is accidentally left behind.

Kevin wakes to find the house empty and the family cars still in the garage, unaware that they had rented vans to take them to the airport. Thinking that his wish has come true, he is overjoyed with his newfound freedom. Later, Kevin becomes frightened by his eccentric next-door neighbor, "Old Man" Marley, rumored to be a serial killer nicknamed the "South-Bend Shovel Slayer" who murdered his own family. The McCallister home is soon stalked by the "Wet Bandits", Harry and Marv, a pair of burglars who have been breaking into other vacant houses in the neighborhood. Kevin tricks them into thinking that his family is still home, forcing them to postpone their plans to rob the McCallister house.

Kate realizes mid-flight that Kevin was left behind, and upon arrival in Paris, the family discovers that all flights for the next two days are booked, and that the phone lines are still down back home in Chicago. Peter and the rest of the family stay at his brother Rob's apartment in Paris while Kate stays at the airport. Unable to book a flight to Chicago, Kate convinces a couple to trade tickets with her. When she eventually arrives in the US, she meets Gus Polinski, the lead member of a traveling polka band, who offers to let her travel with them to Chicago in a moving van on the way to Milwaukee.

On Christmas Eve, Harry and Marv finally realize that only Kevin is in the McCallister home, and Kevin overhears them discussing plans to break into the house that night. He starts to miss his family and asks the local Santa Claus impersonator if he could bring them back for Christmas. Kevin attends a church choir performance, eventually re-encountering Marley, who proves the rumors about himself to be false. Marley points out his granddaughter in the choir and mentions he has never met her since she is the daughter of his estranged son. Kevin suggests he try to reconcile with his son.

Kevin returns home and rigs the house with handmade booby traps. Harry and Marv break in, spring the traps, and suffer various injuries. Kevin calls the police and lures the duo into a vacant neighboring house that they had previously broken into. Harry and Marv ambush Kevin and prepare to get their revenge, but Marley intervenes and knocks them out with his snow shovel. The police arrive and arrest Harry and Marv, having identified all the houses that they broke into due to Marv's habit of flooding them.

On Christmas Day, Kevin is initially disappointed to find that his family is still gone. However, Kate arrives home and they reconcile. The rest of the family then returns after waiting in Paris for a direct flight to Chicago. Kevin keeps sil…

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• Macaulay Culkin as Kevin, an eight-year-old with a penchant for creating harmful inventions
• Joe Pesci as Harry, a thief who targets the McCallisters' home with Marv
• Daniel Stern as Marv, a thief who targets the McCallisters' home with Harry
• John Heard as Peter, Kevin's father
• Roberts Blossom as Old Man Marley, Kevin's eccentric elderly neighbor
• Catherine O'Hara as Kate, Kevin's mother
• Angela Goethals as Linnie, Kevin's older sister
• Devin Ratray as Buzz, Kevin's oldest brother who often gets him into trouble
• Gerry Bamman as Uncle Frank, Peter's rude, cruel, cantankerous, cheap, and selfish older brother and Kevin's uncle
• Hillary Wolf as Megan, Kevin's oldest sister
• John Candy as Gus Polinski, a kind-hearted polka musician who helps Kate
• Larry Hankin as Officer Balzak
• Michael C. Maronna as Jeff, Kevin's older brother
• Kristin Minter as Heather, Kevin's oldest cousin
• Daiana Campeanu as Sondra, Kevin's older cousin
• Jedidiah Cohen as Rod, Kevin's older cousin and Rob's elder son who is living with Uncle Frank and Aunt Leslie
• Kieran Culkin as Fuller, Kevin's youngest cousin
• Senta Moses as Tracy, Kevin's older cousin
• Anna Slotky as Brook, Kevin's younger cousin
• Terrie Snell as Aunt Leslie, Uncle Frank's wife and Kevin's aunt
• Jeffrey Wiseman as Mitch Murphy, eight-year-old neighbor of the McCallisters whom Heather mistakes for Kevin during the headcount
• Virginia Smith as Georgette, Kevin's aunt, wife of Uncle Rob, and mother of Heather, Rod, and Steffan
• Matt Doherty as Steffan, Kevin's older cousin and the son of Rob and Georgette
• Ralph Foody as gangster #1 (Johnny), character in the film Angels with Filthy Souls
• Michael Guido as gangster #2 (Snakes), character in the film Angels with Filthy Souls
• Ray Toler as Uncle Rob, Kevin's uncle, younger brother of Peter and Uncle Frank, and father of Heather, Rod, and Steffan

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Columbus initially hoped to have Bruce Broughton score the film, and early posters listed him as the composer. However, Broughton was busy with The Rescuers Down Under (1990), and he had to cancel at the last minute. Columbus was later able to get in touch with Steven Spielberg, who helped him contact John Williams to produce the final score. Traditional Christmas songs, such as "O Holy Night" and "Carol of the Bells", are featured prominently in the film, as well as the film's theme song "Somewhere in My Memory". The soundtrack was released by Sony Classical Records on cassette on December 4, 1990, and on CD on May 27, 2015.