She began her acting career in films in 1923, appearing in a short film made by Lee De Forest in his Phonofilm sound-on-film process. Her film career continued in Great Britain, most notably in The Private Life of Henry VIII (1933) as Katherine Howard, Henry's fifth wife. Barnes' main qualm in accepting roles as an Actress was that she not play submissive roles. Barnes once remarked "One picture is just like another to me, as long as I don't have to be a sweet woman". Later, her career continued in Hollywood, until 1973, when she appeared in the comedy 40 Carats, her last acting role.
For her contributions to the film industry, Barnes received a motion pictures star on the Hollywood Walk of Fame in 1960. Her star is located at 1501 Vine Street.