Griffith's first feature film was the 1989 sequel The Karate Kid, Part III, in which he played Terry Silver, a rival martial arts expert who influences Daniel LaRusso against his friend and mentor, Mr. Miyagi. In 1996, Griffith starred in the film Hollow Point alongside Tia Carrere, as DEA agent Max Parish and FBI agent Diane Norwood respectively. In the film, they try to find a money launderer who hired a hitman (Donald Sutherland) to kill Diane's FBI partner in revenge for a wedding gone wrong, which resulted in the death of a Russian mobster's son. He also appeared in the 1998 John Carpenter film Vampires as head vampire Jan Valek, and in the 2002 film xXx, in which he portrayed Agent Jim McGrath.
His first TV role was on the soap operaAnother World, as Catlin Ewing, whom he played from 1984 to 1987. In 1999, he starred in the TV movie Secret of Giving with Reba McEntire; earlier in 1999, he had appeared in Reba's video for the song "What Do You Say". He also starred as Rock Hudson in a 1990 TV movie about Hudson's life for which he received critical acclaim. He has made guest appearances on a number of television shows, including In the Heat of the Night, Wiseguy, and One Tree Hill.
Since 2013, Griffith has periodically written for the NBC television series Grimm.