While the novel is told by a third-person narrator in strict chronological order, the film uses voice-over narration (the voice of Mildred). The story is framed by Mildred's interrogation by police after they discover the body of her second husband, Monte Beragon. The film, in noir fashion, opens with Beragon (Zachary Scott) having been shot. He murmurs the name "Mildred" before he dies. The police tell Mildred (Joan Crawford) that they believe the murderer is her first husband, Bert Pierce (Bruce Bennett). Bert has already been interrogated, and confessed to the crime. Mildred protests that he is too kind and gentle to commit murder, and goes on to relate her life story in flashback.
Frank Chambers (John Garfield) is a drifter who stops at a rural diner for a meal and ends up working there. The diner is operated by a beautiful young woman, Cora Smith (Lana Turner), and her much older husband, Nick (Cecil Kellaway).
Tom Reagan is the advisor and right hand man for Leo O'Bannon (Albert Finney), an Irish American mob boss who runs an unspecified eastern city during Prohibition. When Leo's Italian rival Johnny Caspar (John Polito) announces his intent to kill bookie Bernie Bernbaum (John Turturro), Leo goes against Tom's advice and extends his protection to Bernie. Bernie is the brother of Verna Bernbaum (Marcia Gay Harden), who has begun a relationship with Leo while carrying on an affair with Tom.
A former police detective in New Orleans and a recovering alcoholic, Dave Robicheaux is living a quiet life in the swamplands of Louisiana with his wife Annie. The couple's tranquility is shattered one day when a drug smuggler's plane crashes in a lake, right before their eyes.
Private detective Philip Marlowe (Bogart) is summoned to the mansion of his new client General Sternwood (Waldron). The wealthy retired general wants to resolve gambling debts his daughter, Carmen Sternwood (Vickers), owes to bookseller Arthur Gwynn Geiger. As Marlowe is leaving, General Sternwood's older daughter, Mrs. Vivian Rutledge (Bacall), stops him. She suspects her father's true motive for calling in a detective is to find his young friend Sean Regan, who had mysteriously disappeared a month earlier.
Frankie Machine (Frank Sinatra) is released from prison with a set of drums and a new outlook on life, and returns to his run down neighborhood on the North Side of Chicago. A heroin addict, Frankie became clean in prison. On the outside, he greets friends and acquaintances. Sparrow (Arnold Stang), who runs a con selling homeless dogs, clings to him like a young brother, but Schwiefka (Robert Strauss), whom Frankie used to deal for in his illegal card game, has more sinister reasons for welcoming him back, as does Louis (Darren McGavin), Machine's former heroin dealer.
Ann Hamilton (Katharine Hepburn) is a middle-aged bride who begins to suspect that her charming husband Alan Garroway (Robert Taylor) plans to murder her. Nor can she ignore the shadow of her brother-in-law Michael Garroway (Robert Mitchum), whom she's never met but has been told so much about.
At the Central Park Zoo in Manhattan, New York City, Serbian-born fashion designer Irena Dubrovna makes sketches of a black panther. She catches the attention of marine engineer Oliver Reed, who strikes up a conversation. Irena invites him to her apartment for tea. As they walk away, one of Irena's discarded sketches is revealed as a panther impaled by a sword.
High school student Brendan Frye lives a lonely existence following his break up with ex-girlfriend Emily Kostich and the betrayal of his friend Jerr to the authorities. One morning, Brendan discovers a note leading him to a pay phone, where he receives a phone call from a terrified Emily. While begging him for help, she mentions a "brick", "poor Frisco", "Tug", and "the Pin", before abruptly and fearfully hanging up. Her fear appears to have been caused by a passing black Ford Mustang, from which a distinctive-looking cigarette was thrown. Upon asking for information from his acquaintance named Brain, Brendan's search for Emily leads him to Kara, an ex-girlfriend of his - which further leads him to a Halloween party attended by a flirtatious Laura and her boyfriend, Brad Bramish.
After the opening credits, which show a highway's dividing lines at night while blaring techno music plays in the background, Fred Madison (Bill Pullman), a Los Angeles saxophonist, receives a message from an unknown man on the intercom of his house. The voice says that "Dick Laurent is dead." When he looks out his window, the streets outside his house are empty, and faint police sirens are heard in the distance.
On the surface, Richard (Humphrey Bogart) and Kathryn Mason (Rose Hobart) appear to be a happily married couple. But on their fifth wedding anniversary, Kathryn accuses Richard of having fallen in love with her younger sister, Evelyn Turner (Alexis Smith), who is visiting them. He does not deny it, but has resigned himself to leaving things as they are, since he is certain Kathryn would not give him a divorce. At a party celebrating the couple's anniversary hosted by family friend and psychologist Dr. Mark Hamilton (Sydney Greenstreet), Evelyn meets with Mark's handsome young colleague, Professor Norman Holdsworth (Charles Drake). On the way home, Kathryn suggests to Evelyn that their mother is lonely, so Evelyn decides to move home. Distracted by this unwelcome news, Richard crashes their car and suffers a broken leg. He then decides to take desperate action.
The film is set in Fort-de-France, in the French colony of Martinique, in the summer of 1940, shortly after the fall of France. The island is now controlled by pro-German Vichy France. World-weary Harry Morgan (Humphrey Bogart) has a small fishing-boat which he charters to tourists. Eddie (Walter Brennan) is his unofficial mate, though he's not much use due to heavy drinking. Harry is urged to help the French Resistance smuggle some people onto the island, but refuses.
Arthur "Cody" Jarrett (James Cagney) is a ruthless, deranged criminal gang leader. Although married to Verna (Virginia Mayo), Cody is overly attached to his equally crooked and determined mother, "Ma" Jarrett (Margaret Wycherly), his only real confidante (Cody's father died in an insane asylum). Cody suffers from debilitating headaches, and Ma consoles him--even sitting him on her lap and giving him a shot of whiskey with the toast, "Top of the world," an expression she uses more than once.
Vincent Parry, a man convicted of killing his wife, escapes from San Quentin prison by stowing away in a supply truck. He evades police and hitches a ride with a passing motorist named Baker. Parry's odd clothes and a news report on the radio about an escaped convict make Baker suspicious. When questioned, Parry beats him unconscious. Irene Jansen, who had been painting nearby, picks up Parry and smuggles him past a police roadblock into San Francisco, offering him shelter in her apartment.