Born in Metz, France, on January 8, 1933, Jean-Marie Straub initially grew up speaking French, but was forced to learn German at school in the wake of the German occupation. During his studies in Strasbourg and Nancy, which he took up in 1951, he was already the director of a film club in Metz. When he moved to Paris in 1954, he met his future wife Danièle Huillet - the two worked closely together from then on. Also in Paris, Straub got the opportunity to work as an assistant to Jean Renoir, Robert Bresson, Alexandre Astruc and Abel Gance.

In 1956, he assisted Jacques Rivette on his short film "Le coup de Berger". In 1958, Jean-Marie Straub and Danièle Huillet moved to Germany; in 1962 they directed their first short film together, "Machorka-Muff", a rejection of the remilitarization of the Federal Republic. This film, based on a novel by Heinrich Böll, was met with incomprehension by audiences and critics and was also rejected by the selection committee of the IV Oberhausen Short Film Festival. The joint feature film "Nicht versöhnt oder Es hilft nur Gewalt, wo Gewalt herrscht", made in 1964/65 and based on the novel "Billard um halbzehn" by Heinrich Böll, caused a scandal when it was shown at the Berlinale in 1965. The public at large continued to reject the couple's politically barren works in the years that followed. Disputes with commissioning and funding bodies, funding committees, and film review boards were also frequent.

Straub and Huillet, for example, were denied funding for their next work, "Chronicle of Anna Magdalena Bach", which was nevertheless completed in 1967. For the first time, this film showed the complex musical dramaturgy that would also characterize later works of the couple. Nonetheless, the film was again poorly received by audiences, but was awarded Best Film of the Year at the London International Film Festival. At the end of the 1960s, the couple moved to Italy, where they also made their first color film, "Othon" (1969), based on the drama by Corneille.

In the years that followed, Straub/Huillet continued to work on film and adaptations of literary texts, such as "Geschichtsunterricht" in 1972, based on a fragment of Brecht's novel, or, during a fellowship in Hamburg, "Klassenverhältnisse" (DE/FR 1983), based on Kafka's "Amerika-Fragment" ("America Fragment"). The film was shown in competition at the 1984 Berlinale, where it received a Special Mention from the jury.

"Der Tod des Empedokles oder Wenn dann der Erde Grün von Neuem euch erglänzt" (DE/FR 1987) was also invited into the competition of the Berlinale in 1987. During this time, Straub and Huillet directed, among other films, the Hölderlin adaptation "Schwarze Sünde" (DE/FR 1986-89), the documentary "Paul Cézanne im Gespräch mit Joachim Gasquet" (FR/DE 1990), and, for television, the theater film "Antigone" (DE/FR 1992).

In 1996, the couple devoted themselves to a Schönberg opera in "Von heute auf morgen" (FR/DE). This film was awarded the Hessian Film Prize in 1997. Their next feature film, "Sicilia!" (FR/IT 1999), about a Sicilian who returns to his homeland after a long time in New York, screened at the Cannes Film Festival in the Un Certain Regard section and received the Critics' Prize at the São Paulo International Film Festival. "Arbeiter, Bauern" (FR/IT/DE 2001), also shot in Italy, was the pair's last long feature for the time being: apart from the documentary "Une visite au Louvre" (FR/DE 2004), Straub and Huillet made only short films in the next few years.

At the Venice Film Festival in September 2006, where their film "Quei loro incontri" (IT/FR) was shown in competition, Straub and Huillet were honored with a Lifetime Achievement Award. However, there was a scandal at the award ceremony: the two filmmakers were not present but had one of their actors read out a statement written by Straub. Among other things, it said: "As long as imperialist American capitalism exists, there cannot be enough terrorists in the world". This statement caused massive protests, and the jury considered denying Straub and Huillet the prize (but did not). Shortly thereafter, on October 9, 2006, Danièle Huillet died in Cholet, France, at the age of 70.
Jean-Marie Straub remained active as a filmmaker on his own. His most important works in the following years included the feature-length film "Corneille – Brecht" (FR 2009), based on works by Pierre Corneille and Bertolt Brecht, as well as four short films based on works by the Italian poet Cesare Pavese: "Il ginocchio di Artemide" (IT 2008), "Le streghe – Femmes entre elles" (FR/IT 2009), "L'inconsolable" (FR/CH 2011) and "La madre" (CH 2012). Straub's last feature film to was "Communists" (FR/CH), which premiered in Locarno in 2014. One of his last short films, the nine-minute "Où en êtes-vous, Jean-Marie Straub?" (FR 2016), screened in May 2017 as part of a retrospective at the cinema of the DFF - Deutsches Filminstitut & Filmmuseum Frankfurt. In 2020, his last cinematic work was published with the Bernanos adaptation "La France contre les robots".

On November 20, 2022, Jean-Marie Straub died in Rolle, Switzerland, on Lake Geneva.