He was born in Brooklyn, New York City, New York, the son and biographer (2005) of animator Max Fleischer. His film career began in 1942 at the RKO studio, directing shorts, documentaries, and compilations of forgotten silent features, which he called Flicker Flashbacks. He won an Academy Award as producer of the 1947 documentary Design for Death, co-written by Theodor Geisel (later known as Dr. Seuss), which examined the cultural forces that led to Japan's imperial expansion through World War II.

Fleischer directed his first feature in 1946. His early films were taut film noir thrillers such as The Clay Pigeon (1949), Follow Me Quietly (1949), Armored Car Robbery (1950), His Kind of Woman (1951) and The Narrow Margin (1952). In 1954, he was chosen by Walt Disney to direct 20,000 Leagues Under the Sea. He became known for big features, often employing special effects, such as Barabbas (1962), Fantastic Voyage (1966), Dr. Dolittle (1967), and Tora! Tora! Tora! (1970).

Fleischer was perhaps most effective with unpretentious action adventures such as Violent Saturday (1955), Bandido (1956), The Vikings (1958), and Mr. Majestyk (1974). Yet, he had also demonstrated a striking tendency towards social commentary in a trilogy centering on famous serial murderers and focusing on the theme of capital punishment: Compulsion (1959), The Boston Strangler (1968) and 10 Rillington Place (1971). His experience with science fiction films served well in directing the futuristic Soylent Green (1973), a cautionary tale of overpopulation and environmental pollution. Some of his entertainments are regarded as controversial and provocative, such as Che (a biopic of Che Guevara) (1969) and the interracial melodrama of the Deep South in Mandingo (1975).

Fleischer was chairman of Fleischer Studios, which today handles the licensing of Betty Boop and Koko the Clown. In June 2005 he released his telling of his father's career in Out of the Inkwell: Max Fleischer and the Animation Revolution.

He died in his sleep at age 89, after having been in failing health for the better part of a year. Coincidentally, it was the same age at which his father had died.

Fleischer's 1993 autobiography, "Just Tell Me When to Cry," contains many humorous anecdotes about his struggles with actors, writers and producers. Charlton Heston called it one of the best books about how the movie business really works.