Now the Irish actor is delving into his country's blood-soaked past with the Cannes Film Festival entry "The Wind that Shakes the Barley," a historical saga about Ireland's struggle for independence and civil war in the early 1920s.
The film hit close to the heart for Murphy. The action is set on his home turf around Cork in southwest Ireland, where his family lost a cousin in the guerrilla campaign against Britain, which sent in infamous Black and Tan squads to suppress calls for freedom.
"A distant cousin was shot in the back by the Black and Tans and died as they were taking him from safe house to safe house," Murphy told The Associated Press in an interview. "There's a plaque for him down in Cork. He was 17."
Since his breakout role as a Londoner on the run from raging zombies in "28 Days Later," Murphy has become Ireland's next great export behind Guinness, Colin Farrell and Liam Neeson.
Murphy played back-to-back villains last year, as the fear-mongering Scarecrow in "Batman Begins" and the assassination conspirator in "Red Eye." He delivered a gleefully flamboyant performance last fall in Neil Jordan's "Breakfast on Pluto," playing an Irish youth abandoned as a baby who becomes a cross-dressing witness to the explosion of culture and Irish-British violence in the 1970s.
With its eclectic soundtrack, that film allowed Murphy to indulge the old rock star fantasy he's had since youth, when he started out playing in bands.
Murphy also has had roles in "Cold Mountain" and "Girl With a Pearl Earring" and starred in the offbeat ensemble tale "Intermission," which featured his countryman Farrell.
While 2005 was a breakout Hollywood year for Murphy, he said he aims to mix those big American productions with smaller films, including periodic returns to Ireland.
"The people that I admire are like Liam Neeson and Brendan Gleeson (both co-stars in "Breakfast on Pluto"), who manage to work in those big studio movies and yet come back and make very intelligent, very worthwhile smaller films," said Murphy, who turns 30 next week.
"I think it's important to look beyond your Irishness," said Murphy, who now lives in London. "Liam Neeson said to me once, `I'm not an Irish actor. I'm an actor who's Irish.' See what I mean? There's a distinction there, so you can go and play other parts, play American, play British. It's important to do that."
"The Wind that Shakes the Barley" is among 20 films competing for top honors at the Cannes festival, which runs through May 28.
Murphy stars as an Irish medical student whose plans to work at a London hospital are sidetracked when he decides to remain at home and take up arms with his friends and brother against the British troops terrorizing the countryside.
Director Loach, known for working with nonprofessional actors, said Murphy slipped seamlessly into the cast of comparative unknowns.
"He was a huge surprise," Loach said. "He was terrific, he was magnificent, and I wouldn't say this in front of him because it's embarrassing, but he's a man of great integrity and humility in the best sense. I think his integrity is transparent. You can see it in his eyes. He does what he believes in.
"And I think he's convincing as a medical student. He did a bit of research into the doctoring part, and I think he's got a very good bedside manner."
Next up for Murphy — who has been taking time off to spend with his 6-month-old son — is the science fiction tale "Sunshine," reuniting him with "28 Days Later" director Danny Boyle. Murphy plays an astronaut who's part of a team trying to revive the dying sun.
By David Germain