O'Brien's dark good looks belied the fact that she primarily performed comedy roles during the height of her career. This was in part due to her intentionally humorous singing style, which involved her singing with no facial expressions and very little movement - reportedly she stumbed upon this "gimmick" by accident during a stage show when she became virtually paralyzed with stage fright before singing a number. The audience found the performance to be hilarious and she was soon hired to repeat this performance in a number of movies beginning in 1940 for which she gained the nicknames "Frozen Face" and "Miss Ice Glacier" among others. It should be noted that when she wasn't singing, her acting style was just as emotive as other actresses, and she didn't always employ her gimmick when singing as evidenced by her performance in the excerpt of Show Boat in the 1946 film Till the Clouds Roll By.

Among the films she appeared in during her time at MGM were The Big Store (1941) with the Marx Brothers, Ship Ahoy (1942) with Eleanor Powell and Red Skelton, Thousands Cheer (in which she endured ribbing from Mickey Rooney about her singing style), Du Barry Was a Lady (with Skelton and Lucille Ball), The Harvey Girls (with Judy Garland) and Ziegfeld Follies. After appearing once again with Red Skelton in 1947's, Merton of the Movies, and after a guest appearance the following year in the short Musical Merry-Go-Round, O'Brien was suddenly dropped from her MGM film contract and she moved into television and back to live performances.

She only made two film appearances after this: Francis in the Navy and the 1976 Walt Disney Studios comedy, Gus. She continued to perform well into the 1980s with both a one-woman show and a production of Show Boat.