His distinctive square-jaw profile, booming voice, and imposing stature (six-foot-three) has led him to star in many action films, invariably as a bad guy. His first role was playing one of the unfortunate punks who is killed by Arnold Schwarzenegger's character in The Terminator at the beginning of the film.

Thompson also starred as the leader of a gang of serial killers in Cobra alongside another action star, Sylvester Stallone. A more light-hearted role he had was in the comedy movie Three Amigos.

He has also appeared in a wide variety of television shows, such as The X-Files (as the alien bounty hunter) and Buffy the Vampire Slayer, Kindred: The Embraced (as Eddie Fiori, the leader of the Brujah clan), the movie Fright Night Part 2 (where he plays a ghoul), Charmed (as both War from the Four Horsemen of the Apocolypse and the Titan Cronos), and more recently as Admiral Valdore in Star Trek: Enterprise. He also appeared in the earlier Star Trek spin-offs, Star Trek: The Next Generation, Star Trek: Deep Space Nine, as well as the movie Star Trek: Generations.

Cast against his "bad-guy" type, Thompson stars in a family film, Tillamook Treasure (to be released in 2006) as Uncle Jimmy, a rough around the edges Oregon logger. Thompson worked his way through college as a logger so the scenes of axe throwing and pole falling filmed at a real logging show (the Vernonia, Oregon, Logger Show) came naturally to him.

He gathered some bad reputation for his portrayal of Shao Khan in the unpopular video-game movie-sequel Mortal Kombat: Annihilation.

Originally from Washington, Thompson now lives in Los Angeles with his son and daughter.