He is known for playing distressed police officer Jason Dixon in Martin McDonagh’s crime drama Three Billboards Outside Ebbing, Missouri (2017), for which he won the Academy Award for Best Supporting Actor.

Rockwell's other films include The Green Mile (1999), Galaxy Quest (1999), Charlie's Angels (2000), Confessions of a Dangerous Mind (2002), Matchstick Men (2003), The Hitchhiker's Guide to the Galaxy (2005), The Assassination of Jesse James by the Coward Robert Ford (2007), Moon (2009), Gentlemen Broncos (2009), Iron Man 2 (2010), Seven Psychopaths (2012), Jojo Rabbit (2019), and See How They Run (2022).

[4] At age 10, he made a brief stage appearance as Humphrey Bogart in an East Village improv comedy sketch with his mother.

[10] His career slowly gained momentum in the early 1990s, when he alternated between small-screen guest spots in TV series like The Equalizer, NYPD Blue and Law & Order and small roles in films such as Last Exit to Brooklyn and Teenage Mutant Ninja Turtles.

The turning point in Rockwell's career was Tom DiCillo's film Box of Moonlight (1996), in which he played an eccentric man-child who dresses like Davy Crockett and lives in an isolated mobile home.

The ensuing acclaim put him front and center with casting agents and newfound fans alike, with Rockwell himself acknowledging that "That film was definitely a turning point...

"[4] After appearances as a bumbling actor in the science fiction parody Galaxy Quest (1999), as Francis Flute in the Shakespeare adaptation A Midsummer Night's Dream (1999), and as gregarious villain Eric Knox in Charlie's Angels (2000), Rockwell won the then-biggest leading role of his career as The Gong Show host Chuck Barris in George Clooney's directorial debut, Confessions of a Dangerous Mind (2002).

Rockwell also received positive notices for his role opposite Nicolas Cage in Ridley Scott's Matchstick Men (2003), with Entertainment Weekly calling him "destined by a kind of excessive interestingness to forever be a colorful sidekick.

Rockwell eventually appeared in Iron Man 2, released in 2010, as Tony Stark's rival weapons developer, Justin Hammer.

Critic Roger Ebert said of his performance that he "seems to have become the latter-day version of Christopher Walken – not all the time, but when you need him, he's your go-to guy for weirdness.

His performance as a lonely astronaut on a long-term solo mission to the Moon was widely praised, with some critics calling for an Academy Award for Best Actor nomination.

[24][25][26][27] In August 2017, Rockwell was cast to play George W. Bush in Adam McKay's Vice, a biopic of Dick Cheney; he received his second nomination for the Best Supporting Actor Academy Award as a result.

[28][29][30] Rockwell was cast as Bob Fosse with Michelle Williams as Gwen Verdon in the 2019 miniseries Fosse/Verdon, for which he received critical acclaim and a Primetime Emmy Award nomination.

In 2005, Philip Seymour Hoffman directed him in Stephen Adly Guirgis' hit play The Last Days of Judas Iscariot.

Other plays in which Rockwell has performed include: Dumb Waiter (2001), Zoo Story (2001), The Hot L Baltimore (2000), Goosepimples (1998), Love and Human Remains, Face Divided, Orphans, Den of Thieves, Dessert at Waffle House, The Largest Elizabeth in the World, and A Behanding in Spokane.

In 2022, he returned to the Broadway stage in a revival of David Mamet's American Buffalo alongside Laurence Fishburne and Darren Criss.