He remained at Center Stage for some years and often appeared with the late Tana Hicken, most notably as Benedick to her Beatrice in Much Ado About Nothing.

This musical featured five main characters: The Man (played by Jeff Daniels), The Boy (Harold Downs), The Woman (Ann O'Donnell), The Girl (Debbie Penwarden), and The Drunk (James Hilliker), plus a female and a male chorus.

[citation needed] Starting in 1980, O'Quinn has appeared in various feature films such as Silver Bullet, Tombstone, Heaven's Gate, Young Guns, Ghosts of Mississippi, alongside Rutger Hauer in Blind Fury, and as Howard Hughes in The Rocketeer.

When a widowed mother and daughter don't comply with his expectations, he spirals into a spell of madness and attempts to brutally murder them.

He has the thankless assignment of showing us a completely hateful, repellent character – and he approaches the task as an exercise in cloying middle-class good manners.

[9][10] 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 in his new television drama Lost without any audition.

In 2005, O'Quinn received an Emmy nomination for Best Supporting Actor in a Drama for his work as John Locke on the series Lost.

O'Quinn admitted on the TV Guide Channel that he did not have much faith in Lost at first, calling it "The Mysterious Gilligan's Island of Dr.

In February 2021, it was announced that O'Quinn was cast as Martin Queller in the Netflix thriller series Pieces of Her, which is adapted from the Karin Slaughter novel of the same name.

[15] In October 2023, during New York Comic Con, he was announced, to play the antagonist Major General Beale in The Walking Dead The Ones Who Live, created by Scott M. Gimple.