The McCallister family is preparing to spend Christmas in Miami, and gathers at Peter and Kate's Chicago home. Their youngest son, Kevin, sees Florida as contradictory to Christmas, due to its lack of Christmas trees. At a school pageant, Kevin's brother, Buzz, pulls a prank against him, and Kevin retaliates, ruining the pageant. Buzz apologizes, but Kevin berates his family before storming to the attic, wishing to have his own vacation alone. The family accidentally oversleeps again and they rush to make their flight.
At the airport, Kevin loses sight of his family and inadvertently boards a flight to New York City. Arriving there, Kevin decides to tour the city. In Central Park, Kevin sees a homeless lady tending pigeons, which frightens him. Kevin goes to the Plaza Hotel and uses Peter's credit card to check in. Meanwhile, Harry and Marv have traveled to New York after recently escaping from a prison in Illinois, and immediately begin seeking a new target to build up a fortune.
On Christmas Eve, Kevin visits a toy store where he meets its philanthropic owner, Mr. Duncan. Kevin learns that the proceeds from the store's Christmas sales will be donated to a children's hospital, and provides a donation. As a token of appreciation, Mr. Duncan offers Kevin a pair of ceramic turtledoves as a gift, instructing him to give one to another person as a gesture of eternal friendship. After encountering Harry and Marv outside the store, Kevin runs back to the Plaza. The concierge confronts Kevin about the credit card, which has been reported stolen. Kevin flees the hotel, but is ambushed by Harry and Marv, who brag about their plan to kill him and break into the toy store at midnight, just before Kevin escapes.
Landing in Miami, the family discovers that Kevin is missing. After tracking the credit card, they fly to New York. Meanwhile, Kevin goes to his uncle's townhouse, only to find it vacant and undergoing renovations. In Central Park, Kevin encounters the pigeon lady, whom he ultimately befriends. They go to Carnegie Hall, where she explains how her life collapsed when her lover left her. Kevin encourages her to trust people again, and promises to be her friend. After considering her advice that he perform a good deed to make up for his misdeeds, he decides to prevent Harry and Marv from robbing the toy store.
Having rigged the townhouse with booby traps, Kevin arrives at the toy store during Harry and Marv's robbery, takes their picture, and breaks a window, triggering the store's alarm. He then lures them to the townhouse, where they spring the traps and suffer various injuries. While the duo searches for Kevin outside of the townhouse, he calls the police, and lures them into Central Park, where they capture him. The pigeon lady intervenes, and as Kevin escapes, she tosses a bucket of birdseed onto Harry and Marv, attracting a massive flock of pigeons that incapacitate them. Kevin then sets off fireworks to signal the police, who scare off the pigeons with a blanks gunshot, and arrest Harry and Marv. At the toy store, Mr. Duncan finds a note from Kevin, explaining the robbery. Remembering his fondness for Christmas trees, Kate finds Kevin making a wish at the Rockefeller Center Christmas Tree.
On Christmas Day, a truckload of gifts arrive at the McCallisters' hotel room from the toy store. Kevin reconciles with his family, and goes to Central Park to give the pigeon lady the second turtledove, cementing their friendship.
Macaulay Culkin as Kevin, a rambunctious 10-year-old with a penchant for creating harmful inventions
Joe Pesci as Harry, a short, hot-tempered thief
Daniel Stern as Marv, a tall, dim-witted thief
Catherine O'Hara as Kate, Kevin's mother
John Heard as Peter, Kevin's father
Devin Ratray as Buzz, Kevin's oldest brother who often gets him into trouble
Hillary Wolf as Megan, Kevin's oldest sister
Maureen Elisabeth Shay as Linnie, Kevin's older sister; she was previously portrayed by Angela Goethals in the first film
Michael C. Maronna as Jeff, Kevin's older brother
Gerry Bamman as Uncle Frank, Kevin's uncle and Peter's older brother
Terrie Snell as Aunt Leslie, Kevin's aunt
Jedidiah Cohen as Rod, Kevin's older cousin and the older son of Frank and Leslie
Senta Moses as Tracy, Kevin's older cousin and the eldest daughter of Frank and Leslie
Daiana Campeanu as Sondra, Kevin's older cousin and the second daughter of Frank and Leslie
Kieran Culkin as Fuller, Kevin's youngest cousin and the younger son of Frank and Leslie
Anna Slotky as Brooke, Kevin's younger cousin and the youngest daughter of Frank and Leslie
Tim Curry as Mr. Hector (credited as "Concierge"), the concierge at the Plaza Hotel who is suspicious of Kevin
Brenda Fricker as the Pigeon Lady, an unnamed woman who lives in Central Park, spending her life feeding pigeons, who befriends Kevin while he is lost in New York
Eddie Bracken as Mr. Duncan, the proprietor of Duncan's Toy Chest
Dana Ivey as Hester Stone (credited as "Desk Clerk"), the desk clerk at the Plaza Hotel
Rob Schneider as Cedric (credited as "Bellman"), the bellhop at the Plaza Hotel
Leigh Zimmerman as Fashion Model
Ralph Foody as Johnny (credited as "Gangster"), a gangster from the fictional film Angels with Even Filthier Souls, a sequel to Angels with Filthy Souls from the previous film
Clare Hoak as Gangster - "Dame", Johnny's girlfriend from the fictional film Angels with Even Filthier Souls
Monica Devereux as Hotel Operator
Bob Eubanks as Ding-Dang-Dong Host
Rip Taylor as Celeb #1
Jaye P. Morgan as Celeb #2
Jimmie Walker as Celeb #3
Ally Sheedy as New York Ticket Agent
Rod Sell as Officer Bennett
Ron Canada as Cop in Times Square
Donald Trump as himself, owner of the Plaza Hotel. He directs Kevin to the hotel's lobby.