He was the 12th of 13 children born to a Welsh coal miner. He studied acting under Philip Burton, a schoolteacher who became his mentor and helped him obtain a scholarship to the University of Oxford. In gratitude to his benefactor, he assumed the professional name Burton. His first stage appearance was in 1943, but subsequent service as a Royal Air Force navigator delayed his career. In 1948 he resumed his stage performances and had his first role in a motion picture, The Last Days of Dolwyn. He scored his first real stage triumph in 1949 in Christopher Fry's The Lady's Not for Burning.

Burton's first Hollywood film role was in My Cousin Rachel (1952). Throughout the remainder of the 1950s he specialized in historical roles in motion pictures, including the leading role in the first wide-screen CinemaScope production, The Robe (1953). Burton rose to superstar status during the filming of Cleopatra (1963), when he and his American co-star Elizabeth Taylor (Taylor, Dame Elizabeth) became lovers. Both of his highly publicized marriages to Taylor (1964–74, 1975–76) ended in divorce. Who's Afraid of Virginia Woolf? (1966) and The Taming of the Shrew (1967) are the best of the 11 films the couple made together. Burton's other important films include Becket and The Night of the Iguana (both 1964), The Spy Who Came in from the Cold (1965), The Comedians (1967), and Equus (1977).

Burton meanwhile continued to receive critical acclaim for his theatre performances. He acted in Shakespearean productions at London's Old Vic in 1953–56, and he gave a memorable performance of Hamlet in John Gielgud's long-running Broadway production of that play in 1964. Burton also played on Broadway in Jean Anouilh's Time Remembered (1957) and portrayed King Arthur in the Broadway musical Camelot in 1960 and 1980.