Cacoyannis made his first film, "Windfall in Athens" (1953), quickly and on a modest budget; this romantic comedy marked the first of four collaborations with his first muse, the radiant actress Elli Lambetti, and proved popular internationally. In the eyes of some critics, Cacoyannis never did better work than on his first four films; learning as he went, the young director's modest resources and technical limitations if anything added to the finely observed, often harsh studies of Greek family life. As with much postwar European film, Cacoyannis was strongly influenced by Italian neorealism, and he also had the input of gifted cinematographer Walter Lassally, a key figure of the British "Free Cinema" documentary movement. In their studies of small-town maliciousness and harmful bourgeois pride, Cacoyannis' powerful "Stella" (1955, a breakthrough for Melina Mercouri), "A Girl in Black" (1956) and "A Matter of Dignity" (1957) also show his marked, ongoing interest in the tragedies which patriarchy inflicts upon strong women.

Having established himself, Cacoyannis was able to film the screenplay adaptation "Our Last Spring/Eroica" (1960), which had first interested him in filmmaking, and he made his first film abroad with the Italian "The Wastrel" (1961). He received some of the greatest acclaim of his career, and produced one of his finest achievements, with the first installment of what would prove to be a trilogy of Euripides adaptations. "Electra" (1961) evoked the classic tragedy rather than simply adapting it; charged by a powerful central performance by Irene Papas, (with whom he would work regularly over the next 20 years), Cacoyannis made vivid use of violence and harsh environs in telling its anti-heroine's epic tale of woe. He followed up with the considerably more upbeat "Zorba the Greek" (1964), his most famous and popular film. Striking an intriguing balance between the suffering endured by women and an earthy portrait of male bonding, "Zorba" zestfully used Anthony Quinn in the role which would come to overwhelm his image. Though a minority of critics still preferred his earlier work, Cacoyannis had fully arrived as a gifted, recognizable auteur and he received Oscar nominations for Best Director, Best Screenplay and Best Picture.

"The Day the Fish Came Out" (1967), with its cautionary tone and combination of moods from earlier films as it swung from comedy to tragedy, did not find an appreciative audience until years later. Cacoyannis himself became a fish out of water after the 1967 military junta in Greece. Having staged plays in the U.S. and throughout Europe during the 60s, he went into exile and kept busy in this capacity for some years until conditions became more favorable. His only films during this time were the least successful installment in his Euripides trilogy, "The Trojan Women" (1971) and a documentary study of the 1944 Turkish invasion of Cyprus, "Attila 74" (1975). He also made a one-shot venture into the U.S. TV-movie with the well-acted "The Story of Jacob and Joseph" (1974). Upon his return, Cacoyannis seemed to make the final chapter of his trilogy, "Iphigenia" (1977, reteaming him with a passionate Papas), a potent indictment of the abuse of political power.

Never a prolific filmmaker, Cacoyannis was away from the camera for nearly a decade. His theater career continued to flourish as he directed Shakespeare internationally. He also staged a 1983 Broadway revival of the 60s musical "Zorba"; critics were respectful and audiences enjoyed seeing Quinn and Lila Kedrova reprise their lusty goings-on. A return to cinema with the U.S.-made tale of a Chilean family after the fall of the Allende government, "Sweet Country" (1986), flopped, its miscast actors and strange farrago of ingredients failing to evoke the insightful family portraits of his earlier work or the political fervor of his middle period. Cacoyannis kept returning to film in the 90s, though, first for a typically flamboyant comedy of a mother and her gay son, "Up, Down and Sideways" (1993), then back to literary adaptation to take a crack at Chekhov's "The Cherry Orchard" (1999).