Born in Cleveland, Ohio, he was raised in the Greenwich Village section of New York City where his parents ran a bookstore. He graduated from George School in Pennsylvania. He made his film debut in 1961's The Hoodlum Priest, in which he played a juvenile delinquent, though he had an earlier role as the German pilot in a 1960 television adaptation of Mrs. Miniver starring Maureen O'Hara. He played a number of emotionally disturbed youths in films such as David and Lisa (1962) and Bunny Lake is Missing (1965), as well as on television in shows such as Naked City. He appeared with John Huston in the movie De Sade (1969), playing the title role (the Marquis de Sade). He also appeared with Anne Heywood and Sandy Dennis in the 1967 film The Fox. On stage, he starred in the 1975 Broadway play, P. S. Your Cat Is Dead!.

Since the great success of 2001, Dullea has had difficulty reproducing a similar success on film, though he has had a long and successful career on stage in New York City and in regional theaters.

He has a role as a US Senator and a "major influence and mentor" to Matt Damon's character, in Robert De Niro's film The Good Shepherd.

Dullea's other notable roles include Devon in the short-lived 1973 science fiction series The Starlost, Clayton Anderson Jr. in Madame X, Paul Renfield in The Fox, and Thomas Grambell in Brave New World. He also appeared in The Audrey Hepburn Story (starring Jennifer Love Hewitt), as Hepburn's father Joseph.

Dullea has been married to actress Mia Dillon since 1999.