He first appeared on stage in 1918 and also in films from 1919. He worked first in British films then in Hollywood.
After making his first screen appearance in 1920, Brook emerged as a leading British actor in the early 1920s. After moving to the United States, Brook became one of the major stars for Paramount Pictures in the late silent era. During 1928–29 he successfully made the transition to sound and continued to be featured in many of Hollywood's most prestigious films, including a number of literary adaptations. In the mid-1930s he returned to England, where he appeared regularly in leading film roles for a further decade.
One of his best remembered appearances was playing opposite Marlene Dietrich in Shanghai Express (1932). He played Sherlock Holmes three times: The Return of Sherlock Holmes and Sherlock Holmes (in that order), and as part of an anthology film, Paramount on Parade (1930).
In 1934 he was voted one of the most popular stars at the British box office.
In 1943, he adapted the comedy On Approval by Frederick Lonsdale and wrote, produced, directed and starred in the film with Beatrice Lillie, Googie Withers and Roland Culver. The costumes were by Cecil Beaton.
In 1949 he presented the radio series The Secrets of Scotland Yard. In 1956 he appeared on stage in One Bright Day at the Apollo Theatre in London.