Born to two actors who split up when he was five years old, Rockwell was raised in New York and San Francisco. Having already decided in high school that he wanted to follow his parents' footsteps, he had private dramatic training at the William Esper Studios in New York. His career slowly gathered momentum in the early 90s when he alternated between small-screen guest spots in TV shows like The Equalizer, NYPD Blue and Law & Order and small roles in films such as Last Exit to Brooklyn and Teenage Mutant Ninja Turtles.

Rockwell earned critical attention for Tom DiCillo's 1996 film Box of Moon Light, playing an eccentric man-child who dresses like Davy Crockett and lives in an isolated mobile home. He also won strong reviews for the 1997 film Lawn Dogs, where he played a working-class lawn mower who befriends a wealthy 10-year-old girl (played by Mischa Barton) in an upper-class gated community in Kentucky; Rockwell's impressive performance won him Best Actor honors at both the Montreal World Film Festival and the Catalonian International Film Festival. After strong appearances as a psychotic killer in the Stephen King prison drama The Green Mile and a bumbling actor in the sci-fi satire Galaxy Quest (both 1999), Rockwell won the biggest leading role of his career to date: the troubled and controversial The Gong Show host Chuck Barris in actor George Clooney's 2002 directorial debut, Confessions of a Dangerous Mind. Starring alongside established Hollywood stars like Drew Barrymore and Julia Roberts, Rockwell earned the lion's share of critics' praise, though the film was not a box-office success.

Since then he's won further good notices for his comic role opposite Nicolas Cage in Ridley Scott's 2003 comedy Matchstick Men, and played Zaphod Beeblebrox in the 2005 film version of The Hitchhiker's Guide to the Galaxy.