The son of ethnic Serbians, Serbedzija was born and raised in Croatia where he first gained prominence as both a stage and screen actor. (With the dissolution of Yugoslavia in the early 1990s, he and his family were forced to flee to Belgrade, Serbia.) After a 1964 visit to the USA, he enrolled in drama school. Small parts on stage followed for many years until his 1974 breakthrough performance as "Hamlet" in Dubrovnik made him a star. Although he continued to appear in theatrical productions (notably, "Peer Gynt" and "Oedipus Rex"), Serbedzija broke into films around the same time. Although many of the more than 40 features he has made in the 70s and 80s have been little-seen outside of Yugoslavia, a handful have received widespread distribution. His early work included the starring role in "Uziska Republica" (1974), but it was probably not until his turn as the captain interrogating a woman who rescued hundreds of children from the Holocaust in "Hanna's War" (1988) that he was noticed in the West. US art-houses booked "Manifesto" (1988), an impish ensemble piece about life in a Balkan community overrun with assassination attempts and sexual freedoms. In 1996, Serbedzija played the refugee father in "Belma" and a New Zealand immigrant who wants his daughter to marry a wealthy Chinese man, not the Maori with whom she has fallen in love in "Broken English".
Serbedzija is also known for his poetry readings and has released four albums. On the London stage, he won critical praise for his work in Colin Redgrave's Moving Theatre Company staging of "Brecht in Hollywood" (1994).