Isaak's music can be described as a blend of country, blues, rock and roll, pop and surf rock.  He signed a contract to Warner Bros. Records in 1984 for his first album Silvertone. Isaak's contract was renewed in 1988 when Warner Bros. moved him to their Reprise Records label.  His best-known song is "Wicked Game." Though released on the 1989 album Heart Shaped World, an instrumental version of the song was later featured in the David Lynch film Wild at Heart (and also years later in the 2000 film The Family Man). Lee Chesnut, an Atlanta radio station music director who was obsessed with David Lynch films, began playing the full version and it quickly became a nationwide top ten hit. The music video for the song was directed by Herb Ritts and was a big MTV and VH1 hit; shot in black and white, it starred Isaak and model Helena Christensen rolling on the beach, embracing and whispering in each others' ears. Another less-seen version of the "Wicked Game" is directed by David Lynch and comprises scenes from the film Wild at Heart.

Isaak has also appeared in numerous films, mostly playing minor cameo roles, though he starred with Keanu Reeves and Bridget Fonda in the 1993 Bernardo Bertolucci-directed Little Buddha, and also played a major role in David Lynch's Twin Peaks: Fire Walk with Me (1992). Other motion pictures include Married to the Mob (1988), The Silence of the Lambs (1991), That Thing You Do! (1996), and A Dirty Shame (2004). He also guest-starred on the "The One After the Superbowl, Part One" - the Super Bowl XXX edition of the television sitcom Friends; and on the HBO miniseries, From the Earth to the Moon.  See Chris Isaak LIVE!  Purchase your Chris Isaak tickets today!