Powers had great success in his first Broadway appearance, as William Booth in "Mr. Lazarus" (1916). He became a star in musical comedies, and won acclaim as a leading player and character actor. His best-known roles included Gregers Werle in "The Wild Duck", the captain in "Androcles and the Lion", and Bluntschli in "Arms and the Man" — all in 1925 — and King Magnus in "The Apple Cart" (1930). He created the role of Charles Marsden in Eugene O'Neill's long-running drama, "Strange Interlude" (1928–29). In 1938 he succeeded Orson Welles as Brutus in the Mercury Theatre's debut stage production, "Caesar", and in 1941 he toured nationwide in "The Man Who Came to Dinner". His last significant Broadway role was in "Three Sisters" (1942), with Judith Anderson, Katharine Cornell and Ruth Gordon.