Eustache was born in Pessac, Gironde, France into a working class family. Relatively little information exists about Eustache’s life prior to the time he became a member of the Cahiers du cinema crowd in the late fifties, though it is known that he was largely self-educated and worked in the railroad service prior to becoming a filmmaker. Information suggests that the mystery surrounding his youth was intentional, with sources stating that "during his lifetime Eustache published little information about his early years, indicating that he felt no nostalgia for an unhappy childhood." .
Though not a member of the Nouvelle vague, Eustache maintained ties to it, appearing as an actor in Jean-Luc Godard's Week End and editing Luc Moullet's Une aventure de Billy le Kid, which starred Jean-Pierre Leaud (the lead in Eustache's The Mother and the Whore).
After becoming a filmmaker, Eustache maintained close ties to his friends and relatives in Pessac. In 1981, he was partially immobilized in an auto accident. He killed himself in his apartment Paris, a few weeks before his 43rd birthday.
Eustache had a son, Boris Eustache (b. 1960), who worked on his father's second feature and appears as an actor in Eustache's short film Les Photos d'Alix.
Eustache was quoted as saying, “The films I made are as autobiographical as fiction can be.” Because of his reticence to discuss his personal life, it is assumed that his body of work was largely autobiographical. Besides his fictional shorts and features, Eustache made numerous documentaries, many of them very personal, including several shot in his hometown of Pessac and a feature-length interview with his grandmother.
Eustache directed two narrative features. The first, The Mother and the Whore (La maman et la putain), is a three-hour-and-forty-minute rumination on love, relationships, men and women. The film’s central three-way romance plot focuses on Alexandre (Jean-Pierre Léaud), his girlfriend Marie (Bernadette Lafont) and the nurse he meets and falls in love with, Veronika (Françoise Lebrun).
Eustache’s second feature, Mes petites amoureuses (1974), was intentionally different from his debut. Shot in color 35mm by acclaimed cinematographer Nestor Almendros (as opposed to The Mother and the Whore's grainy black-and-white), the film also features significantly less dialogue and focuses on teenage characters in a rural setting.
Eustache admired the documentary qualities of early actuality films, and frequently cited the Lumiere Brothers as influences. He made two films about a religious parade in Pessac, both titled La Rosière de Pessac, in 1968 and 1979, and remade his short Une sale histoire twice. Regarding the tendency to re-examine in Eustache's work, the American film critic Jonathan Rosenbaum wrote: "An obsessive-compulsive filmmaker and clearly a tormented one who wound up dying by his own hand, Eustache was clearly experimenting with his variations as well as goading viewers into examining their own reactions to them."