Byrne started his acting career with Ireland's world renowned Abbey Theatre, later joining London's Royal Court Theatre and the Royal National Theatre, where he played leading roles before moving to the United States.

On Broadway, he received a Tony nomination for his performance in Eugene O'Neill's "Moon for the Misbegotten" and won the Outer Critics Circle Award for Best Actor for his performance in another O'Neill play, "A Touch of the Poet."

Byrne has worked with some of the cinema's leading directors, including the Coen Brothers, Wim Wenders, Jim Jarmusch, Ken Loach, John Boorman, David Cronenberg and Bryan Singer. He has starred in more than 35 feature films including, Excalibur, Miller's Crossing, Into the West, The Point of No Return, Little Women, The Usual Suspects, Dead Man, The End of Violence, The Man in the Iron Mask, Vanity Fair, Jindabyne and Wah-Wah, etc.

His television credits include HBO’s Weapons of Mass Distraction and In Treatment. For his work on In Treatment, Gabriel has been nominated twice for an Emmy and received the Golden Globe in 2009. His producing credits include the Academy Award nominated In the Name of the Father, Into the West and is currently producing Tent City with Oprah Winfrey. He is the author of Pictures In My Head — a memoir.