His father Dan was a soldier and cooper, while his mother Eileen (née Gannon), from Elphin, County Roscommon,[4] was a hospital nurse.

[6] He attended University College Dublin, where he studied archaeology, Spanish and linguistics, and graduated with a BA in 1972,[7] becoming proficient in the Irish language.

[12] Before becoming an actor, Byrne had many jobs, including archaeologist, cook, and Spanish and history school teacher at Ardscoil Éanna in Crumlin.

[7] In 1983, Byrne appeared with Richard Burton in the miniseries Wagner, co-starring Laurence Olivier, John Gielgud and Ralph Richardson.

Byrne was cast in a film adaptation of Flann O'Brien's metafictional novel At Swim-Two-Birds, alongside Colin Farrell and Cillian Murphy.

He was named as TV's "latest Dr. McDreamy" by The New York Times[19] for this role, and won the Golden Globe Award for Best Actor in a Drama Series in 2008.

In 2011, Byrne signed up to appear in a film by director Costa-Gavras, Le Capital,[20] an adaptation of Stéphane Osmont's novel of the same name.

In 2017, Byrne appeared in Mad to Be Normal (previously titled Metanoia), a biopic of the Scottish psychiatrist R. D. Laing, produced by Gizmo Films.

[21] Walking with Ghosts, Byrne's one-man show based on his memoir of the same title (published by Grove Press in January 2021), premiered at the Gaiety Theatre, Dublin on 1 February 2022,[22] before playing at the Edinburgh International Festival.

[30] At the fifth Jameson Dublin International Film Festival in 2007, Byrne was presented with the first of the new Volta awards, for lifetime achievement in acting.

[31] Byrne released a documentary for the 20th Galway Film Fleadh in the summer of 2008 called Stories from Home, an intimate portrait about his life.

[35] Byrne also criticised the marketing strategy employed by Guinness known as Arthur's Day as "a cynical piece of exercise in a country which has a huge drinking problem".