A major impact on his life was Orson Welles, whom he met in 1936 when they both had roles in the Broadway production of Sidney Kingsley's Ten Million Ghosts.

His films in this period included For Whom the Bell Tolls (1943), Between Two Worlds (1944), Mr. Skeffington (1944) and Watch on the Rhine (1943), in which he repeated the role he originated in the Broadway production.

Coulouris was the first actor to star in the title role of the Bulldog Drummond radio program on the Mutual Broadcasting System.

[8] After his return in 1950 Coulouris joined the Bristol Old Vic company for its Spring season, appearing as Tartuffe, Brutus and Sir John Brute, among other roles.

Later film roles included parts in The Heart of the Matter (1953), Doctor in the House (1954), Papillon (1973), Mahler and Murder on the Orient Express (both 1974).

In Me and Orson Welles (2008), Richard Linklater's period drama set in the days surrounding the premiere of the Mercury Theatre's production of Caesar, Coulouris is portrayed by Ben Chaplin.