On a Thursday, an alcoholic New York writer, Don Birnam (Ray Milland), is packing for a weekend vacation with his brother Wick (Philip Terry), who is trying to discourage his drinking. When Don’s girlfriend Helen (Jane Wyman) comes to see them off, she mentions that she has two tickets for a concert, to which Don urges Wick to accompany her. Don heads for Nat’s Bar, deliberately missing his train, and then sneaks back into the flat to drink some cheap whisky he has bought, avoiding Helen, who is worried about his being left alone.
On Friday, back at the bar, the owner, Nat (Howard Da Silva), criticizes Don for treating Helen so badly, and Don recalls how he first met her. It was due to a mix-up of cloakroom tickets at the opera-house, where he had to wait for the person who had been given his coat-check in error. This was Helen, with whom he strikes up a romance. When he is due to meet her parents for lunch at a hotel, he loses his nerve and phones a message to her, crying off. Presently he confesses to her that he is two people: "Don the writer", whose fear of failure causes him to drink, and "Don the drunk" who always has to be bailed out by his brother. Still, Helen devotes herself to helping him in his plight. Back in the present day, Don has moved on to another bar, where he is caught stealing money from a woman's purse to pay his bill, and he is promptly thrown out of the establishment by its staff. Back in his flat, he finds a bottle he had stashed in a light fixture the previous night and drinks himself into a stupor.
On Saturday, Don is broke and all the pawnshops are closed for Yom Kippur. At Nat’s Bar, he is refused service. Desperate for money, he visits a girl who has had a long-held crush on him, but stood her up during this latest binge. Leaving her flat, he falls down the stairs and is knocked unconscious.
On Sunday, Don wakes up in an alcoholics' ward where "Bim" Nolan (Frank Faylen), a cynical male nurse, mocks him and other guests at "Hangover Plaza", but he offers to help cure his delirium tremens. Don refuses help and then manages to escape from the ward while the staff are occupied with a raving, violent patient.
On Monday, still broke, Don steals a bottle of whisky from a store and spends the day drinking and hallucinating. Helen returns, alerted by a call from Don's landlady who can hear his screams. Finding him collapsed and in a delirious state, she vows to look after him and stays overnight on his couch.
On Tuesday morning, Don slips out and pawns Helen’s coat—the thing that had first brought them together—in order to buy a gun. She trails him to the pawn shop and learns from the pawnbroker that he traded the coat for a gun he had pawned earlier. She races to Don's apartment and interrupts him just before he is about to shoot himself in the bathroom. He tells her their relationship is over as she catches a glimpse of the gun lying in the bathroom sink. Helen rushes to sink, grabs the weapon, but he quickly pries it out of her hand. She reminds Don of her love for him, and her concern that he should stop drinking. Nat then arrives to return Don's portable typewriter, which the bartender says he found "floating around in the Nile" and warns him not to "hock her". After Nat leaves, Helen is finally able to convince him that "Don the writer" and "Don the drunk" are the same person. He finally commits to writing his novel The Bottle, dedicated to her, which will recount the events of the weekend. He drops a cigarette into a glass of whiskey to make it undrinkable, as proof that he is cured.
Wilder was originally drawn to this material after having worked with Raymond Chandler on the screenplay for Double Indemnity. Chandler was a recovering alcoholic at the time, and the stress and tumultuous relationship with Wilder during the collaboration caused him to start drinking again. Wilder made the film, in part, to try to explain Chandler to himself.
The film was intended to have no musical score, but preview audiences laughed at what they considered Milland's overwrought performance, and the studio brought in Miklós Rózsa who wrote an original score for the picture. Upon release, the film was a success. The film's musical score was among the first to feature the theremin, which was used to create the pathos of alcoholism.
The film also made famous the "character walking toward the camera as neon signs pass by" camera effect.
Rights to the film are currently held by Universal Studios, which owns the pre-1950 Paramount sound feature film library via EMKA, Ltd.
Billy Wilder originally wanted Jose Ferrer for the role of Don, but he turned it down. Charles Brackett's first choice for playing Helen was Olivia de Havilland, but she was involved with a lawsuit that prevented her from being in any film at that time. It has been said that Katharine Hepburn and Jean Arthur were also considered for the role.
The film differs significantly from the book by leaving out the novel's noted homosexual overtones, namely the strong implication that Don Birnam, just like the book's author Charles Jackson, is a closet homosexual.
The film was a commercial success. Produced on a budget of $1.25 million, it grossed $11,000,000 at the box office, earning $4.3 million in US theatrical rentals.
In 2011, The Lost Weekend was deemed "culturally, historically, or aesthetically significant" by the United States Library of Congress and selected for preservation in the National Film Registry. The Registry said the film was "an uncompromising look at the devastating effects of alcoholism" and that it "melded an expressionistic film-noir style with documentary realism to immerse viewers in the harrowing experiences of an aspiring New York writer willing to do almost anything for a drink."
At the 18th Academy Awards in May 1946, The Lost Weekend received seven nominations and won in four categories.
This film also shared the 1946 Grand Prix du Festival International du Film at the first Cannes Film Festival and Milland was awarded Best Actor. To date, The Lost Weekend and Marty (1955) are the only films ever to win both the Academy Award for Best Picture and the highest award at the Cannes Film Festival. (Marty received the Palme d'Or (Golden Palm), which, beginning at the 1955 festival, replaced the Grand Prix du Festival International du Film as the highest award.)
The Lost Weekend was adapted as a radio play on the January 7, 1946 broadcast of The Screen Guild Theater, starring Milland, Wyman, and Faylen in their original film roles.
On March 10, 1946, three days after winning the Academy Award, Milland appeared as a guest on a radio broadcast of The Jack Benny Show. In a spoof of The Lost Weekend, Milland and Jack Benny played alcoholic twin brothers. Phil Harris, who normally played Jack Benny's hard-drinking bandleader on the show, played the brother who tried to convince Ray and Jack to give up liquor. ("Ladies and gentlemen," said an announcer, "the opinions expressed by Mr. Harris are written in the script and are not necessarily his own.") In the alcoholic ward scene, smart-aleck Frank Nelson played the ward attendant who promised Ray and Jack that they would soon start seeing DT visions of strange animals. When the DT visions appeared (with Mel Blanc providing pig squeals, monkey chatters, and other animal sound effects), Ray chased them off. "Ray, they're gone!" Benny shouted. "What did you do?" Milland replied, "I threw my Oscar at them!"