By the late 1950s, Dern had taken the stage on Broadway, and by the early '60s, he was appearing on TV and in films. After landing supporting roles in movies such as Roger Corman's The Trip and They Shoot Horses, Don't They? Dern assumed the lead in a series of '70s films, including Silent Running, The King of Marvin Gardens, The Great Gatsby and Coming Home (which earned him an Oscar nod).
More recent films for Dern include All the Pretty Horses (2000) and Monster (2003). In 2006, Dern joined the cast of HBO's polygamy drama "Big Love."