- Macaulay Culkin as Kevin McCallister, an eight-year-old with a penchant for creating harmful inventions
- Joe Pesci as Harry Lyme, a thief who targets the McCallisters' home with Marv
- Daniel Stern as Marv Murchins, a thief who targets the McCallisters' home with Harry
- John Heard as Peter McCallister, Kevin's father
- Roberts Blossom as Marley, Kevin's elderly neighbor
- Catherine O'Hara as Kate McCallister, Kevin's mother
- Angela Goethals as Linnie McCallister, Kevin's older sister
- Devin Ratray as Buzz McCallister, Kevin's oldest brother who often gets him into trouble
- Gerry Bamman as Uncle Frank McCallister, Peter's rude, cruel, cantankerous, cheap, and selfish older brother
- Hillary Wolf as Megan McCallister, Kevin's oldest sister
- John Candy as Gus Polinski, a kind-hearted polka musician who helps Kate
- Larry Hankin as Officer Larry Balzak
- Michael C. Maronna as Jeff McCallister, Kevin's older brother
- Kristin Minter as Heather McCallister, 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 McCallister, 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 McCallister, Uncle Frank's wife
- Jeffrey Wiseman as Mitch Murphy, an 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 and Steffan
- Matt Doherty as Steffan, Kevin's older cousin
- 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 and Steffan
- Billie Bird as Woman in Airport, Irene, who sells Kate her ticket to Dallas
- Bill Erwin as Man in Airport, Ed, Irene's husband who agrees with Irene's ticket sale
- Gerry Becker as Officer #1
- Alan Wilder as Scranton Ticket Agent
- Hope Davis as French Ticket Agent
- Kenneth Hudson Campbell as Santa, man in a Santa Claus suit whom Kevin meets
- Jim Ortlieb as Herb the drugstore clerk
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