Clarke was born Violet Mary Klotz in Philadelphia, Pennsylvania. Her father was a theater organist. She studied dancing as a child and began on stage in vaudeville and also worked in night clubs.  Clarke started her professional career as a dancer in New York City, sharing a room with Barbara Stanwyck. She subsequently starred in many films for Universal Studios, including the original screen version of The Front Page (1931) and the first sound version of Frankenstein (1931) with Boris Karloff. Clarke played the role of Henry Frankenstein’s fiancee Elizabeth in Frankenstein, who was attacked by the Monster (Karloff) on her wedding day.  The Public Enemy, released that same year, contained one of cinema’s most famous (and frequently parodied) scenes, in which James Cagney pushes a half grapefruit into Clarke’s face, then goes out to pick up Jean Harlow. The film was so popular that it ran 24 hours a day at a theater in Times Square upon its initial release; Clarke’s ex-husband had the grapefruit scene timed and would frequently buy a ticket, enter the theater to again enjoy that sequence, then immediately leave the theater.

Clarke appeared as Myra Deauville in the 1931 Pre-Code version of Waterloo Bridge. In the film she portrays a young American woman who is forced by circumstance into a life of prostitution in World War I London; both the film and Clarke’s performance were well received by the critics.  Clarke also appeared in the modest pre-code Universal film Night World (1932), with Lew Ayres, Boris Karloff, Hedda Hopper, and George Raft.  By the mid-1930s, Clarke was no longer a leading lady and was only featured in small parts through to the 1960s. In the early 1930s Clarke’s face had been left partially scarred as a result of a car crash, recounts G. Mank in his Frankenstein film saga book It’s Alive. (He also writes that Mae would attend Frankenstein fan club events during her senior years.) In 1949 Clarke was the female lead of Republic Pictures’ 12-chapter movie serial King of the Rocket Men that introduced their popular atomic rocket-powered hero.  On television, Clarke acted in the series Perry Mason and Batman (episode 48).  Clarke was married and divorced three times: to Fanny Brice’s brother Lew Brice, Stevens Bancroft, and Herbert Langdon. All the unions were childless. Clarke died from cancer on April 29, 1992, at age 81, in Woodland Hills, California. She is buried in Valhalla Memorial Park Cemetery.