Born in London to a Jewish family, he went on to work in television as an actor after graduating from the Balliol College, Oxford. One of his first movies, the documentary Terminus (1960), earned him a Venice Film Festival Gold Lion and a British Academy Award.

His first three movies, A Kind of Loving (1962), Billy Liar (1963) and Darling (1965) describe tartly the modern urban way of life in England. Schlesinger's next movie was Far From the Madding Crowd (1967), an adaptation of Thomas Hardy's popular novel. Schlesinger's Midnight Cowboy (1969) was internationally acclaimed and it won Oscars for Best Director and Best Picture.

His later films include Sunday Bloody Sunday (1971), The Day of the Locust (1975), Marathon Man (1976), Yanks (1979), Pacific Heights (1990), A Question of Attribution (1991), and The Innocent (1993).

Schlesinger also directed Timon of Athens (1964) for the Royal Shakespeare Company and the musical I and Albert (1972) at London's Piccadilly Theatre. From 1973 he was an associate director of the Royal National Theatre.

Schlesinger underwent a quadruple heart bypass in 1998, before suffering a stroke in December 2000. He was taken off life support at Desert Regional Medical Center in Palm Springs on July 24, 2003 and died early the following day.