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".
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), 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.
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. Although not a classicist by training, she 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 professor Kevin Kopelson, "...Renault mischaracterize[s} pederastic relationships as heroic."
On April 18, 2006, UK, BBC 4 aired a one hour documentary, Mary Renault – Love and War in Ancient Greece, with this description:
Mary Renault died at Cape Town, South Africa, on 13 December, 1983.