The son of a tannery worker, Sillitoe worked in factories from the age of 14. In 1946 he joined the air force and for two years served as a radio operator in Malaya. After his return to England, X-rays revealed that he had contracted tuberculosis, and he spent several months in a hospital. Between 1952 and 1958 he lived in France and Spain; in Majorca he met the poet Robert Graves (Graves, Robert), who suggested that he write about Nottingham. Sillitoe began work on his first published novel, Saturday Night and Sunday Morning (1958; filmed 1960). An immediate success, it is the story of a rude and amoral young labourer for whom drink and sex on Saturday night provide the only relief from the oppression of the working life. From the short-story collection The Loneliness of the Long Distance Runner (1959), Sillitoe helped adapt the title story into a film (1962). Later novels, such as The Death of William Posters (1965) and The Widower's Son (1977), deal with more intellectual working-class characters. Notable short-story collections are The Ragman's Daughter (1963; filmed 1974), Men, Women, and Children (1974), and The Second Chance (1980).

Sillitoe has also written children's books, poetry, and plays while continuing as a novelist. Life Without Armour, an autobiography, was published in 1995.