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O'Quinn began acting in the 1970s. He has appeared in such films as Tombstone, Heaven's Gate, The Rocketeer, and as the deranged serial killer in The Stepfather. His early television roles include guest appearances on Miami Vice (episode "Give a Little, Take a Little"), Earth 2, Moonlighting, Star Trek: The Next Generation (episode "The Pegasus"), The New Twilight Zone (episode "Chameleon"), Homicide: Life on the Street (episode "Hate Crimes"), and a recurring role as Rear Admiral Thomas Boone on JAG. In 1995, O'Quinn began a series of notable guest appearances in The X-Files, Millennium, and Harsh Realm, all produced by Chris Carter, who also cast him in the film The X-Files: Fight The Future. After a string of recurring appearances on Alias (2002–2003), as the FBI Director Kendall, O'Quinn became a favorite of television producer J.J. Abrams. Following a seven-episode guest run on The West Wing in 2003–2004, O'Quinn received a call from Abrams indicating that the producer wanted to cast him, with no audition needed, in his new television drama Lost[citation needed]. In 2005 and 2007, O'Quinn received an Emmy nomination for Best Supporting Actor in a Drama for his work as John Locke on Lost. O'Quinn admitted on the TV Guide Channel that he did not have much faith in the series Lost at first, calling it "The Mysterious Gilligan's Island of Dr. Moreau." On September 16, 2007, he won an Emmy Award for Outstanding Supporting Actor In A Drama Series for his role in Lost.