He was born in Addis Ababa, Ethiopia and spent his early years between Ethiopia and Greece. In 1939 he established himself in Paris and worked as an extra in films. Eventually, he owned the famous Parisian club 'La Rose Rouge' where performers included singer Juliette Greco. He was married to actress Anouk Aimée from 1951 to 1954 and from whom he had a daughter, Manuela Papatakis, born in 1951. He was then married to actress Olga Karlatos from 1967 to 1982, from whom he had a son, Serge Papatakis, born in 1967.

In 1957, Papatakis moved to New York City, met John Cassavetes, and became co-producer of Cassavetes' Shadows (1959). In 1963, his first film, Les Abysses, enjoyed a "Succès de scandale" and was entered into the 1963 Cannes Film Festival which refused to show it.[4] It was based on Jean Genet's The Slaves. In 1967, he directed another daring film, Oi Voskoi (The Shepherds in Greek). During the Algerian War he was active in the Front de Liberation National. He returned to filmmaking in 1987 with a film in Greek, I Photografia (The Photograph). His last movie was Walking a Tightrope (1992).

Papatakis died in Paris on 17 December 2010.