He has guest starred in number of notable television series namely, MacGyver, Cold Case, Quantum Leap, Murder, She Wrote, Chicago Hope, Roseanne, Six Feet Under, Criminal Minds and many other series. O'Bryan also had starring roles in the sitcoms Pig Sty, Brother's Keeper and Abby, all of which were canceled after their first seasons.

O'Bryan's film credits include Chaplin, Crimson Tide, Phenomenon, Exit to Eden, Out to Sea, Big Fat Liar, Deck the Halls, Yes Man and both Princess Diaries films.

In 2010, O'Bryan co-starred in the NBC series Persons Unknown. In 2007, he guest-starred in Criminal Minds in the episode, 'Ashes and Dust' as Vincent Stiles, a serial killer/serial arsonist who goes around killing innocent people at night.