In 1960 Ganz landed his first film role, in Der Herr mit der schwarzen Melone (The Man in the Black Derby). Despite the support of lead actor Gustav Knuth, Ganz's cinematic debut was not particularly successful and it was only many years later that his career in film got off the ground. Ganz made his film breakthrough in a major part in the 1976 film Sommergäste [de], launching a widely recognized film career in Europe and the United States. He worked with several directors of the New German Cinema like Werner Herzog and Wim Wenders, and also with international directors like Éric Rohmer and Francis Ford Coppola, among others. In 1977, he co-starred with Dennis Hopper in Wenders' American Friend, an adaptation of Patricia Highsmith's novel Ripley's Game, playing a terminally ill father who gets hired as a professional killer. In 1979, he starred opposite Klaus Kinski in Herzog’s Nosferatu: Phantom der Nacht (Nosferatu: Phantom of the Night). Ganz played a professor opposite Sir Laurence Olivier in the thriller The Boys from Brazil (1978), about Nazi fugitives.