In Friendship, Maine, young boys Nicky and Andreas enter Whipstaff Manor on a dare, but are scared away by a ghost named Casper.
Meanwhile, following the death of her father, neurotic and spoiled heiress Carrigan Crittenden discovers she has only been left Whipstaff Manor in his will. Carrigan and her assistant, Dibs, find a map within the will's papers that alleged treasure hidden inside the manor, but find the property haunted by Casper and his obnoxious prankster uncles, the Ghostly Trio, and unsuccessfully attempt to force the ghosts out by way of paranormal experts and a demolitions team. A lonely Casper watches a news report about paranormal therapist James Harvey and is instantly smitten with his teenage daughter, Kat, prompting Casper to inspire Carrigan in summoning Dr. Harvey to Whipstaff. Harvey and Kat are estranged due to his reputation and obsession with contacting the ghost of his late wife, Amelia. The Harveys move into Whipstaff, but Casper's attempt to befriend them fails when his uncles try to scare them away.
Casper gains the Harveys' trust when he serves them breakfast, and follows Kat to school, where she becomes popular when her class learns she is living in Whipstaff, and agrees to host their Halloween party. Her envious classmate Amber plots with her boyfriend, Vic, to humiliate Kat during the party. Harvey attempts therapy sessions with the Ghostly Trio, who reveal they know Amelia; in exchange for convincing Carrigan to leave them alone, they promise to go through the "red tape" involved to get Harvey a meeting with his wife.
Kat learns Casper has no memory of his life, and restores his old playroom to remind him. Casper recognizes an old wooden[sled his father bought him, and remembers playing outside until he caught a severe cold and died of pneumonia, becoming a ghost to keep his father company. A newspaper article reveals that Casper's father was declared insane after he built a machine, the Lazarus, which he claimed could bring the dead back to life. Casper and Kat venture to the basement and find the Lazarus. Carrigan and Dibs sneak inside, steal the formula that powers the Lazarus, and plot to use the machine, believing it could grant them immortality. However, they attempt to kill each other to test the theory and retrieve the treasure they think is in the basement's locked vault; Carrigan falls off a cliff to her death, and rises as a ghost.
Dr. Harvey becomes despondent after the trio prank him, prompting them to eat sweeties and take him out on the town. They plan on killing him to make themselves a quartet, but have a change of heart after a drunken Harvey declares he will tell Carrigan off so they can stay in their home. However, Harvey accidentally falls to his death down a manhole.
In the laboratory, Carrigan confronts Casper and Kat, stealing what she believes to be the treasure from the vault and launching Dibs out a window when he tries to double-cross her. Casper and Kat trick Carrigan into stating that she has no unfinished business on Earth, causing her to be ejected into the afterlife. The treasure is revealed to be Casper's prized baseball, signed by Duke Snider; the so-called map was part of a game Casper played with his father. Dr. Harvey, now a ghost, returns with Casper's uncles, and Kat’s despair over this prompts Casper to sacrifice his one chance to return to life, restoring her father instead.
The Halloween party kicks off upstairs, and Amber and Vic’s prank is thwarted by the Ghostly Trio, and they flee in terror. A dejected Casper is visited by the angel of Amelia, who rewards him for his selflessness by temporarily transforming him into a human boy. Casper dances with Kat, while Amelia meets with Harvey and tells him that she was so content with her family while alive that she has no unfinished business, and encourages him to move on. Amelia departs as the clock chimes ten and, after kissing Kat, Casper transforms back into a ghost, scaring off the guests. Kat is impressed with the party, which Harvey says is not over, cuing the Ghostly Trio to play their nephew's theme for them to dance to.
- Malachi Pearson as the voice of Casper McFadden, a lonely ghost, who was originally a 12-year-old boy who died of pneumonia. He spends most of his afterlife in Whipstaff dealing with his ghostly ghoulish uncles' antics while hoping to find a friend. He finds one in Kat, while also developing a crush on her.
- Devon Sawa as Casper McFadden (human form)
- Christina Ricci as Kathleen "Kat" Harvey, James' 13-year-old daughter and Casper's love interest, who has lost her mother and wants to make a friend.
- Bill Pullman as Dr. James Harvey, Kat's father; a ghost therapist interacting with the 'living impaired', helping them to cross into the next dimension while hoping to find his deceased wife.
- Joe Nipote as the voice of Stretch, the leading member of the Ghostly Trio and one of Casper's uncles who bonds with Dr. Harvey.
- Joe Alaskey as the voice of Stinkie, the second member of the Ghostly Trio and one of Casper's uncles who bonds with Dr. Harvey.
- Brad Garrett as the voice of Fatso, the third member of the Ghostly Trio and one of Casper's uncles who bonds with Dr. Harvey.
- Cathy Moriarty as Catherine "Carrigan" Crittenden, a glamorous, treacherous and greedy woman upset about her late father's only leaving Whipstaff to her in his will, until she discovers that the house contains treasure, and hires Dr. Harvey to exorcise the ghosts in order to get it.
- Eric Idle as Paul "Dibs" Plutzker, Carrigan's assistant.
- Garette Ratliff Henson as Vic DePhillippi, Kat's crush and Amber's boyfriend.
- Jessica Wesson as Amber Whitmire, Kat's rival and Vic's girlfriend.
- Amy Brenneman as Amelia Harvey, James's deceased wife and Kat's deceased mother.
- Ben Stein as Rugg, Carrigan's lawyer.
- Chauncey Leopardi and Spencer Vrooman as Nicky and Andreas, two preteen boys who explore Whipstaff in the opening scene.
- Don Novello as Father Guido Sarducci
- Dan Aykroyd as Ray Stantz
- Fred Rogers
- Terry Murphy
- Clint Eastwood
- Rodney Dangerfield
- Mel Gibson
- John Kassir as the Crypt Keeper
- Brock Winkless performed the puppetry for the Crypt Keeper in the film
- Steven Spielberg (deleted scenes)
- Jess Harnell as the voice of Arnold
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