Boyd began in British films, but it was his role in a 1957 French film Les bijoutiers du clair de lune (English title: Heaven Fell That Night) opposite Brigitte Bardot that got him noticed. He went to Hollywood and appeared as second leads in a variety of films. His role as Messala in Ben-Hur (1959) propelled him to international fame and he was thereafter fated to play roles wearing breastplates and Roman togas, as in Samuel Bronston's The Fall of the Roman Empire (1964), in which he co-starred with Sophia Loren. He was originally chosen to play Mark Antony opposite Elizabeth Taylor in 20th Century-Fox's epic production of Cleopatra under the direction of Rouben Mamoulian, but eventually withdrew from the problem-plagued production when he committed to star in The Fall of the Roman Empire (Cleopatra was later directed by Joseph L. Mankiewicz and the role of Mark Antony went to Richard Burton).

Boyd also appeared in John Huston's Biblical epic The Bible...in the Beginning (1966) and was top-billed in another costumed epic Genghis Khan (1965), filmed in Yugoslavia. He appeared in the French-produced Napoleonic epic Imperial Venus (1962), playing opposite Gina Lollobrigida. His non-epic roles included the musical Billy Rose's Jumbo (1962) opposite Doris Day, the Hollywood melodrama The Oscar (1966), the sci-fi special effects extravaganza Fantastic Voyage (1966), the spy thriller Assignment K (1969) and the international Western Shalako (1969), shot in Spain. His career declined in the 1970s and he appeared in several European potboilers before making a comeback in Michael Apted's British gangster thriller The Squeeze (1977).

He died of a heart attack at the age of 45 while playing golf.

Stephen Boyd was interred in Oakwood Memorial Park Cemetery in Chatsworth, California.