His first feature film was Andy in 1965. His greatest success as a feature film director came with Vanishing Point, an existential road movie that followed a man driving a white Dodge Challenger from Denver to San Francisco in 15 hours; critics disliked the movie, but it became a cult hit.
His television career began in the early 1960s in Kansas City as Altmans assistant. Sarafian soon began to direct television shows, and in 1963, he scored one of his great successes as director of the "Living Doll" episode of The Twilight Zone.