Michael "Mike" Enslin is a cynical, skeptical author who is estranged from his wife Lily after the death of their daughter Katie. Mike writes niche books evaluating supernatural events in which he has no belief. After his latest book, he receives an anonymous postcard depicting The Dolphin, a hotel on Lexington Avenue in New York City, bearing the message: "Don't enter 1408." Viewing this as a challenge, Mike arrives at The Dolphin and requests room 1408.
The hotel manager, Gerald Olin, attempts to discourage him. He explains to Mike that in the last 95 years, no one has lasted more than an hour inside of Room 1408; the latest count is 56 deaths. Olin attempts to dissuade and bribe Mike, but Mike insists, threatening legal action against the hotel, so preparations are reluctantly made.
Inside the room, Mike describes on his mini-cassette recorder the room's boring appearance and lack of supernatural behavior. The clock radio suddenly starts playing "We've Only Just Begun", a hit song by The Carpenters and the digital display changes to a countdown starting from "60:00." Mike begins to see ghosts of the room's past victims, followed by flashbacks of Katie and his sick father. Mike tries to leave, but all attempts are in vain.
Mike uses his laptop to contact Lily, asking for help, but the sprinkler system short circuits his laptop. The room temperature drops to subzero when the laptop suddenly begins to work again. A doppelgänger of Mike appears in a video chat window and urges Lily to come to the hotel room herself; it gives Mike a sly wink. The room shakes violently and Mike breaks a picture of a ship in a storm. Water pours from the broken picture, flooding the room. He surfaces on a beach and relives a surfing accident seen earlier in the film. His life continues from this point, and he reconciles with Lily.
Assuming his experience in 1408 was just a nightmare, Lily encourages him to write a book about it. When visiting the post office to send the manuscript to his publisher, he recognizes members of a construction crew as Dolphin Hotel staff. The employees then destroy the post office's walls, revealing that Mike is still trapped in the rubble of 1408. Katie's ghost confronts him, and when the countdown ends, the room is suddenly restored to normal, and the clock radio resets itself to 60:00.
The "hotel operator" calls Mike. Mike asks why he has not been killed yet and she informs him that guests enjoy free will: he can relive the past hour over and over again, or use their "express checkout system". A hangman's noose appears, but he refuses to give in. Deciding to quit running, Mike improvises a Molotov cocktail and sets the room on fire. The hotel is evacuated. After smoking a cigarette, Mike breaks a window, causing a backdraft. He then lies down and laughs in victory upon destroying the room. Olin, in his office, praises Mike for his actions.
John Cusack as Michael "Mike" Enslin
Samuel L. Jackson as Gerald Olin
Mary McCormack as Lily Enslin
Tony Shalhoub as Sam Farrell
Len Cariou as Mike's father
Jasmine Jessica Anthony as Katie Enslin
Isiah Whitlock Jr. as Hotel Engineer
Kim Thomson as Hotel Desk Clerk
Benny Urquidez as Claw Hammer Maniac
Angel Oquendo as Taxi Cab Driver
Andrew-Lee Potts as Mailbox Guy
Jules de Jongh as the Female Front-Desk Voice on the Phone (Uncredited)
based on Stephen King's 1999 short story of the same name