Cloete was born in Paris, France to a French mother and South African father. He was educated at Lancing College, and the school gives out a yearly prize in his honour to a student who excels in literature and creative writing. He lived most of his adult life in the town of Hermanus, in the Western Cape. He published his first novel, Turning Wheels, in 1937: it became a best-seller, selling more than two million copies. Importation of the book was subsequently banned in South Africa, owing to its commentary on the Great Trek, the event in which the book is set.

Many of his 14 novels and most of his short stories are historically based fictional adventures, set against the backdrop of major African, and, in particular, South African historical events. Apart from Turning Wheels, another prominent novel, 1963's Rags of Glory, is set during the Boer war (with, according to its foreword, much of the historical information based on Rayne Kruger's Goodbye Dolly Gray.) Two of his novels were turned into movies: The Fiercest Heart (1961) is based on his 1955 novel of the same name, and Majuba, released in 1968, is based on his 1941 novel The Hill of the Doves.

His short stories are also much-acclaimed. He published at least eight volumes in his lifetime.

In addition to producing South-African related works, Cloete was among the pioneers of the by-now voluminous literary sub-genre depicting the aftermath of nuclear war. His 1947 novelette The Blast is written as the diary of a survivor living in the ruins of New York (published in 6 Great Short Novels of Science Fiction, ed. Groff Conklin, 1954).

Other written genres to which he contributed included poetry (collected in a volume published in 1941, The Young Men and the Old) and biography (African Portraits, 1946).

He published the first part of his autobiography, A Victorian Son, in 1972 and the second, The Gambler, in 1973. Stuart Cloete died on 19 March 1976, in Cape Town, South Africa.

Following Cloete's death, the copyright to his works passed to his widow, Tiny Cloete. After her death in August, 1993, the copyright passed to Cloete's American-South African friend Warren Wilmot Williams. Although Cloete never wished to have any children of his own, he regarded Williams as an "adopted" son. In the late 1960s Cloete was instrumental in launching the young Williams' career as a documentary film producer and media executive. After inheriting the Stuart Cloete literary estate, Warren Williams established a trust to hold the copyright to Cloete's works. The copyright is managed by the British-based company Stuart Cloete Print Holdings Ltd.

Novels

• Turning Wheels, 1937
• Watch for the Dawn, 1939
• Yesterday is Dead, 1940
• The Hill of Doves, 1941
• The Young Men and the Old, 1941
• Congo Song, 1943
• The Curve and the Tusk, 1953
• The Fiercest Heart, 1955
• Mamba, 1956
• The Mask, 1957
• Gazella, 1958
• Rags of Glory, 1963
• The Abductors, 1966
• How Young they Die, 1969

Short story collections

• Christmas in Matabeleland, 1942
• The third way, 1947
• The soldiers' peaches, and other African stories, 1959
• The silver trumpet, and other African stories, 1961
• The looking glass, and other African stories, 1963
• The thousand and one nights of Jean Macaque, 1964
• The honey bird, and other African stories, 1964
• The writing on the wall, and other African stories, 1968
• Three white swans; and other stories, 1971
• The company with the heart of gold, and other stories, 1973
• More nights of Jean Macaque, 1975
• Canary pie, 1976

Non-fiction

• African portraits: a biography of Paul Kruger, Cecil Rhodes and Lobengula, last King of the Matabele, 1946
• Against these three, 1947
• The African giant: the story of a journey, 1955
• Storm over Africa: a study of the Mau Mau Rebellion, its causes, effects, and implications in Africa south of the Sahara, 1956
• West with the sun, 1962
• South Africa: the land, its people and achievements, 1968
• A Victorian son: an autobiography, 1897-1922, 1972
• The gambler: an autobiography volume 2, 1920-1939, 1973