Born at Dacre Lodge, 49 Plashet Road, Forest Gate, Essex, (now Greater London), Renault was educated at St Hugh's College of Oxford University, then an all-women's college, receiving a undergraduate degree in English in 1928. In 1933, she began training as a nurse at Oxford's Radcliffe Infirmary. During her training, she met Julie Mullard, a fellow nurse with whom she established a life-long romantic relationship.

She worked as a nurse while beginning a writing career, treating Dunkirk evacuees at the Winford Emergency Hospital in Bristol, and working in Radcliffe Infirmary's brain surgery ward until 1945. She published her first novel, Purposes of Love, in 1939; it had a contemporary setting, like her other early novels, which novelist Linda Proud described as "a strange combination of Platonism and hospital romance". Her 1943 novel The Friendly Young Ladies, about a lesbian relationship between a writer and a nurse, seems inspired by her own relationship with Mullard.

In 1948, after her novel Return to Night won a MGM prize worth $150,000, she and Mullard emigrated to South Africa, where they remained for the rest of their lives. There, according to Proud, they found a community of gay expatriates who had "escaped the repressive attitudes towards homosexuality in Britain for the comparatively liberal atmosphere of Durban.... Mary and Julie found themselves able to set up home together in this new land without causing the outrage they had sometimes provoked at home." (Renault and Mullard were critical of the less liberal aspects of their new home, participating in the Black Sash movement against apartheid in the 1950s.)

It was in South Africa that Renault was able to write forthrightly about homosexual relationships for the first time ... in her last contemporary novel, The Charioteer (1953), the story of two young gay servicemen who fall in love during World War II, and then in her first historical novel, The Last of the Wine (1956) , the story of two young Athenians who study under Socrates and fight against Sparta. Both these books had male protagonists, as did all her later works that included homosexual themes; her sympathetic treatment of love between men would win Renault a wide gay readership. It would also foster rumors that Renault was really a gay man writing under a female pseudonym. Renault found these rumors amusing, but also sought to distance herself from being labeled a "gay writer."

Her subsequent historical novels were all set in ancient Greece, including a pair of novels about the mythological hero Theseus and a trilogy about the career of Alexander the Great. In a sense, The Charioteer ... the story of two young gay servicemen during World War II who try to model their relationship on the ideals expressed in Plato's Phaedrus and Symposium ... is a warm-up for Renault's historical novels. By turning away from the 20th century and focusing on stories about male lovers in the warrior societies of ancient Greece, Renault no longer had to deal with homosexuality and antigay prejudice as social "problems"; instead she was free to focus on larger ethical and philosophical concerns while examining the nature of love and leadership. (Ironically, The Charioteer could not be published in the U.S. until 1959, after the success of The Last of the Wine proved that American readers and critics would accept a serious gay love story.)

Although not a classicist by training, Renault was admired in her day for her scrupulous recreations of the Greek world. Some of the history presented in her fiction (and in her nonfiction work, The Nature of Alexander) has been called into question: her novels about Theseus rely on the controversial theories of Robert Graves, and her portrait of Alexander has been criticized as uncritical and romanticized. According to Kevin Kopelson, professor of English at the University of Iowa, Renault "mischaracterize[s] pederastic relationships as heroic." Renault defended her interpretation of the available sources in author's notes attached to her books, and even her critics generally credit her with providing a vivid portrait of life in ancient Greece.

Defying centuries of admiration for Demosthenes as a great orator, Renault portrayed him as a cruel, corrupt and cowardly demagogue.

Though Renault appreciated her gay following (and the income it provided), she was uncomfortable with the "gay pride" movement that emerged in the 1970s after the Stonewall riots. Like Laurie Odell, the protagonist of her 1953 novel The Charioteer, she was suspicious of identifying oneself by one's sexual orientation. Late in her life, she expressed hostility toward the gay rights movement, troubling some of her devoted fans.

On April 18, 2006, BBC Four aired a one hour documentary about the author's life entitled Mary Renault — Love and War in Ancient Greece.

Mary Renault died at Cape Town, South Africa, on 13 December 1983.

Contemporary fiction

• Purposes of Love (US title: Promise of Love) (1939)
• Kind Are Her Answers (1940)
• The Friendly Young Ladies (US title: The Middle Mist) (1943)
• Return to Night (1947)
• The North Face (1948)
• The Charioteer (1953)

Historical novels

• The Last of the Wine (1956) — set in Athens during the Peloponnesian War; the narrator is a student of Socrates
• The King Must Die (1958) — the mythical Theseus up to his father's death
• The Bull from the Sea (1962) — the remainder of Theseus' life
• The Mask of Apollo (1966) — an actor at the time of Plato and Dionysius the Younger (brief appearance by Alexander near the end of the book)
• Fire from Heaven (1969) — Alexander the Great from the age of four up to his father's death
• The Persian Boy (1972) — from Bagoas's perspective; Alexander the Great after the conquest of Persia
• The Praise Singer (1978) — the poet Simonides of Ceos
• Funeral Games (1981) — Alexander's successors

Nonfiction

• The Nature of Alexander (1975) — a biography of Alexander the Great
• Lion in the Gateway: The Heroic Battles of the Greeks and Persians at Marathon, Salamis, and Thermopylae (1964) — about the Persian Wars

Radio

The King Must Die and The Bull From the Sea have been adapted as an 11-part BBC Radio 4 serial entitled The King Must Die.