L'histoire se déroule aux États-Unis en 1962. Frank Vallelonga, surnommé "Tony Lip", un videur italo-américain de New York, cherche un emploi après la fermeture de la Copacabana, la boîte de nuit où il travaillait, pour rénovations. Il est invité pour une entrevue par le docteur Don Shirley, un excentrique pianiste noir d'origine jamaïcaine, qui cherche un chauffeur pour une tournée de huit semaines à travers le Midwest et le Sud profond. Don engage Tony grâce à ses références. Ils partent et prévoient de revenir à New York pour le Réveillon de Noël. Le label de Don donne à Tony une copie du Green Book, un guide pour les voyageurs afro-américains indiquant des motels, des restaurants et des stations-service qui autorisent la visite de personnes de couleur.
In Paris in 1910, mother cat Duchess and her three kittens, Marie, Berlioz, and Toulouse, live with retired opera diva Madame Adelaide Bonfamille, and her English butler, Edgar. While preparing her will with lawyer Georges Hautecourt, Madame declares her fortune to be left to her cats until their deaths, and thereafter to Edgar. Edgar hears this through a speaking tube, and plots to eliminate the cats. Therefore, he sedates the cats by sleeping pills in their food, and enters the countryside to abandon them. There, he is ambushed by two hounds, named Napoleon and Lafayette, and the cats are stranded in the countryside, while Madame Adelaide, Roquefort the mouse, and Frou-Frou the horse discover their absence. In the morning, Duchess meets an alley cat named Thomas O'Malley, who offers to guide her and the kittens to Paris. The group briefly hitchhike in a milk cart before being chased off by the driver. Later, while crossing a railroad trestle, the cats narrowly avoid an oncoming train, but Marie falls into a river and is saved by O'Malley; himself rescued by two English geese, Amelia and Abigail Gabble, who accompany the cats to Paris. Edgar returns to the country to retrieve his possessions from Napoleon and Lafayette, as the only evidence that could incriminate him.
The film opens with a montage of images of Manhattan and other parts of New York City accompanied by George Gershwin's Rhapsody in Blue, with Isaac Davis (Woody Allen) narrating drafts of an introduction to a book about a man who loves the city. Isaac is a twice-divorced, 42-year-old television comedy writer dealing with the women in his life who quits his unfulfilling job. He is dating Tracy (Mariel Hemingway), a 17-year-old girl attending the Dalton School. His best friend, college professor Yale Pollack (Michael Murphy), married to Emily (Anne Byrne), is having an affair with Mary Wilkie (Diane Keaton). Mary's ex-husband and former teacher, Jeremiah (Wallace Shawn), also appears. Isaac's ex-wife Jill Davis (Meryl Streep) is writing a confessional book about their marriage. Jill has also since come out of the closet as a lesbian and lives with her partner, Connie (Karen Ludwig).
Set against the backdrop of the Cold War and Soviet political repression of the early 1980s prior to perestroika, Vladimir Ivanoff (Robin Williams), a saxophonist with the Moscow circus, lives in a crowded apartment with his extended family. He stands in lines for hours to buy toilet paper and shoes. When the apparatchik assigned to the circus (Kramarov as Boris) criticizes Vladimir for being late to rehearsal and suggests Vladimir may miss the approaching trip to New York, Vladimir gives Boris a pair of shoes from the queue that made Vladimir late.
In 1936, New York City, Billie Holiday is arrested on a drugs charge.
In a flashback to 1928, Billie is working as a housekeeper in a brothel where she is raped. She runs away to her mother, who sets up a job cleaning for another brothel in the Harlem section of New York. The brothel is run by an arrogant, selfish owner who pays Billie very little money.
The film begins with a scene set in Brooklyn, New York in 1969. A group of four boys walk up to Bleek Gilliam's brownstone and ask him to come out and play baseball with them. Bleek's mother insists that he continue his trumpet lesson, to his chagrin. His father becomes concerned that Bleek will grow up to be a sissy, and a family argument ensues. In the end, Bleek continues playing his trumpet, and his friends go away.
Andrew Neiman is a first-year jazz student at the prestigious Shaffer Conservatory in New York. He has been playing drums from a young age and aspires to become one of the greats like Buddy Rich. Famed conductor Terence Fletcher discovers Andrew practicing in the music room late one night and eventually invites him into his studio band as the alternative for core drummer Carl Tanner. Fletcher is abusive toward his students, mocking and insulting them; when the band rehearses the Hank Levy piece "Whiplash" and Andrew struggles to keep his tempo, Fletcher hurls a chair at him, slaps him, and berates him in front of the class.
Dave Garver (Clint Eastwood) is a KRML radio jockey who broadcasts nightly from a studio in Carmel-by-the-Sea, California, often incorporating poetry into his program. He lives a rather freewheeling bachelor lifestyle. At his favorite bar, seemingly by coincidence, he encounters a woman named Evelyn Draper (Jessica Walter). Dave drives Evelyn home, where she reveals that their meeting was not coincidental; she deliberately sought him out after hearing the bar mentioned on his radio show. He guesses correctly that she is a recurring caller who always requests the jazz standard "Misty." The two have sex.
The film follows big band leader Glenn Miller (1904–1944) (James Stewart) from his early days in the music business in 1929 through to his 1944 death when the airplane he was flying in was lost over the English Channel during World War II. Prominent placement in the film is given to Miller's courtship and marriage to Helen Burger (June Allyson), and various cameos by actual musicians who were colleagues of Miller.
While driving his Dual-Ghia from Las Vegas to Los Angeles, lecherous, heavy-drinking pop singer Dino (Dean Martin) is forced to detour through Climax, Nevada. There he meets the amateur songwriting team of Barney Millsap (Cliff Osmond), a gas station attendant, and piano teacher Orville J. Spooner (Ray Walston), a man easily given to jealousy. Hoping to interest Dino in their songs, Barney disables the "Italian" sports car and tells Dino he will need to remain in town until new parts arrive from Milan. (Dual-Ghia was actually an American marque, mating a Dodge frame, drivetrain, and engine with Italian coachwork.
Jazz cornetist Pete Kelly (Webb) and his Big Seven are the house band at the 17 Club, a speakeasy in Kansas City in 1927 during Prohibition. New local crime boss Fran McCarg (Edmond O'Brien) wants a percentage of the band's meager earnings. Despite the band's opposition, Kelly wisely gives in.
American World War II veteran Jerry Mulligan (Gene Kelly) is now an exuberant expatriate in Paris trying to make a reputation as a painter. His friend and neighbor, Adam Cook (Oscar Levant), is a struggling concert pianist who is a longtime associate of a French singer, Henri Baurel (Georges Guétary). At the ground-floor bar, Henri tells Adam about his cultured girlfriend. Jerry joins them later, before going out to sell his art.