Born August 10, 1971 in Washington, D.C., Theroux came from an artistic family. His uncle, Paul, wrote The Mosquito Coast, while his cousin, Louis, is a journalist. He discovered acting while attending Buxton School, a boarding school in Williamstown, MA (after being expelled from several high schools). Theroux graduated from Bennington College with a double major in visual arts and drama and later attended the prestigious British American Drama Academy in London, England.

Theroux made his film debut in 1996, in Mary Harron's I Shot Andy Warhol. Since then, he has performed both in comedies, such as The Baxter, Romy and Michelle's High School Reunion, Broken Hearts Club and Zoolander, and darker, more serious fare such as American Psycho and Mulholland Drive, widely considered to be his breakout movie. Charlie's Angels: Full Throttle has been his most successful film, in terms of box office receipts. He will appear next in the film versions of the cult TV show Strangers With Candy and Michael Mann's Miami Vice. Some think he has take the place of Kyle MacLachlan as Lynch's doppelgänger/Protagonist, as he is now starring in Lynch's new film Inland Empire. He is also rumored to be in the running to appear as Two-Face in the sequels to Christopher Nolan's Batman Begins, and is developing a script, Tropic Thunder, that his friend Ben Stiller has rumored to have been signed on to.

Theroux also has an extensive television resume, having appeared on episodes of shows such as Alias, Sex and the City and Six Feet Under.