Duras was born Marguerite Donnadieu on April 4, 1914 in Gia-Dinh (a former name for Saigon), Cochinchina, French Indochina (now Vietnam); she was the only daughter of two teachers who responded to a campaign by the French government encouraging French people to settle in the colony.

In the 1940s, Duras became an active member of the PCF (the French Communist Party).

At 17, Duras went to France, her parents' native country, where she began studying for a degree in mathematics. She soon abandoned this to concentrate on political science, then law. After completing her studies, through 1941, she worked for the French government in the Ministry of the Colonies; in the 1930s she also changed her name to Marguerite Duras during this period. She married in 1939 to the Writer Robert Antelme.

During World War II, from 1942 to 1944, Duras worked for the Vichy government in an office that allocated paper quotas to publishers (in the process operating a de facto book-censorship system), but she was also a member of the French Resistance as a part of a small group that also included François Mitterrand, who later became President of France and remained a lifelong friend of Duras. During the war, Antelme was deported to Buchenwald in 1944 for his involvement in the Resistance, and barely survived the experience (weighing on his release, according to Duras, just 38 kg). She nursed him back to health, but they divorced once he recovered his health.

In 1943, for her first published novel Les Impudents, she decided to use as pen name the surname of Duras, a village in the Lot-et-Garonne département, where her father's house was located.

Other major works include Moderato Cantabile (1958), which was the basis of the 1960 film Seven Days... Seven Nights; Le Ravissement de Lol V. Stein (1964); and her play India Song, which Duras herself later directed as a film in 1975. She was also the Screenwriter of the 1959 French film Hiroshima mon amour, which was directed by Alain Resnais. Duras's early novels were fairly conventional in form, and were criticized for their "romanticism" by fellow Writer Raymond Queneau; however, with Moderato Cantabile, she became more experimental, paring down her texts to give ever-increasing importance to what was not said. She was associated with the nouveau roman French literary movement, although she did not belong definitively to any one group. She was noted for her command of dialogue.

Many of her works, such as Le Ravissement de Lol V. Stein and L'Homme assis dans le couloir (1980), deal with human sexuality. Her films are also experimental in form; most eschew synchronized sound, using voice over to allude to, rather than tell, a story; spoken text is juxtaposed with images whose relation to what is said may be more-or-less indirect. Despite her success as a Writer, Duras's adult life was also marked by personal challenges, including a recurring struggle with alcoholism. In 1983 she was awarded the Grand Prix du Théâtre de l’Académie française.

Duras was the author of many novels, plays, films, interviews, essays, and works of short fiction, including her best-selling, highly fictionalized autobiographical work L'Amant (1984), translated into English as The Lover, which describes her youthful affair with a Chinese man. It won the Goncourt prize in 1984. The story of her adolescence also appears in three other books: The Sea Wall, Eden Cinema and The North China Lover. A film version of The Lover, produced by Claude Berri and directed by Jean-Jacques Annaud, was released to great success in 1992. Duras's novel The Sea Wall was first adapted into the 1958 film This Angry Age by René Clément, and again in 2008 by Cambodian Director Rithy Panh as The Sea Wall.

Duras died of throat cancer in Paris in 1996, aged 81. Her funeral, held in the packed church of Saint-Germain-des-Prés, was highlighted with several musical recordings, including a piano version of "India Song". She is buried in Montparnasse Cemetery.