Donald O'Brien's early life was marked by his family's flight from France to Ireland during World War II due to the Nazi occupation. Born in Pau, France, O'Brien's Irish father, a former US Army Calvary officer who fought in the Spanish-American war, and his English mother, a governess, fled to Ireland where Donald would his spend formative years.
He studied acting under the renowned Irish theatre legend Micheál MacLiammóir, and later moved back to France where he worked various odd jobs including a prizefighter and office worker.
Donald O'Brien made his feature film debut in 1953 at the age of 23 in Anatole Litvak's war drama Act of Love. A chance meeting with director John Frankenheimer led to him being cast as a Nazi officer in The Train in 1964, which impressed the director so much that he cast him in a supporting role in Grand Prix in 1966.
In 1967, O'Brien was brought to Italy to star in Sergio Sollima's cult Spaghetti Western Run, Man, Run in 1968. His portrayal of ex-American lawman turned soldier of fortune Nathaniel Cassidy led to future leading roles in the genre for a number of years, during which he changed his name from "Donal" to "Donald" due to contracts frequently misspelling it.
Donald O'Brien quickly became a staple of Italian B-movies, appearing in a wide range of films including Spaghetti Westerns, horror films, and Sexploitation pictures. In 1981, he starred in Zombie Holocaust, which earned him a strong cult following among horror and exploitation film fans for his portrayal of the eponymous mad scientist.
However, that same year he sustained a brain injury that paralyzed half his body, and significantly reduced the number of roles he could play even after he recovered. He appeared in several films for the notorious Joe D'Amato, and had a supporting role as a Franciscan friar opposite Sean Connery in Jean-Jacques Annaud's The Name of the Rose in 1986.
Following another accident in 1996, O'Brien all but retired from acting, settling in Paris with his family.
