Roth was born Timothy Simon Smith in Dulwich, London, the son of Anne, a painter and teacher, and Ernie Smith, a journalist and member of the British Communist Party. Roth has German Jewish heritage. His father adopted the surname Roth after World War II in order to hide his nationality when traveling in countries hostile to the British. He attended Strand School in Tulse Hill. As a young man, Roth wanted to be a sculptor and studied at London's Camberwell School of Art.

After some time at the Camberwell School of Art, Roth tried acting and made his debut at the age of 21 playing a white power skinhead in a TV movie entitled Made in Britain. Roth played an east end character in 'King of the ghetto' which was made by the BBC. This four part drama was shown in 1986 on national television, based on a novel by Farukh Dhondy. The story partly set in Brick Lane, caused a sensation among the public, especially amongst the bengali community. Sadly there has been no mention of this drama since its first broadcast. In 1984, Roth played an apprentice hitman in Stephen Frears' The Hit with Terence Stamp and John Hurt, earning an Evening Standard Award for Most Promising Newcomer. With that recognition, he appeared in several other films during the end of the decade. In 1989 he had a memorable supporting role as the buffonish lackey, Mitchell, in Peter Greenaway's The Cook, the Thief, His Wife & Her Lover. In 1990, Roth began to enjoy international attention with starring roles as Vincent Van Gogh in Robert Altman's Vincent & Theo and Guildenstern in Tom Stoppard's Rosencrantz & Guildenstern Are Dead. Roth impressed director Quentin Tarantino and was cast as Mr. Orange in his 1992 ensemble piece Reservoir Dogs. This film paved the way for more work in Hollywood. In 1994, Tarantino cast him again as a robber in the acclaimed Pulp Fiction. They worked again in the 1995 flop Four Rooms. However, Roth returned to the successful road playing viciously evil English nobleman Archibald Cunningham in Rob Roy opposite Liam Neeson. For that role he won an Oscar nomination for Best Supporting Actor, a Golden Globe nomination, and a British Academy Award. In 1996, he went a different way, starring with Drew Barrymore in Woody Allen's musical comedy Everyone Says I Love You. He also starred as Danny Boodman T.D. Lemon 1900 (or just "1900") in the movie The Legend of 1900. In 1999 he made a critically acclaimed debut as a director with The War Zone, a film of Alexander Stuart's novel. In 2001, he made another important move by portraying General Thade in Tim Burton's Planet of the Apes. He was also considered for the part of Hannibal Lecter in the 2001 film Hannibal had Anthony Hopkins not returned to the role. Roth recently appeared in Francis Ford Coppola's Youth Without Youth and Michael Haneke's Funny Games. He will play opposite Edward Norton in The Incredible Hulk, as Emil Blonsky.

Roth had a son Jack with Lori Baker in 1983. He married Nikki Butler in 1993, and had 2 sons with her: Timothy Hunter (b. 1995) and Cormac (b. 1996). Both of his sons with Butler are named after the couple's favorite authors: Hunter S. Thompson and Cormac McCarthy.