Though she made her first film appearance in 1913, her Hollywood career began in earnest in 1931 and lasted until 1957. In her films she often played the wife of Guy Kibbee (Footlight Parade, Wonder Bar, Mr. Smith Goes to Washington). Among her roles was the part of Sister Michael in The Bells of St. Mary's, starring Bing Crosby and Ingrid Bergman. Years after her final film role, she returned to the stage, understudying Patsy Kelly in the Broadway revival of No No Nanette with old co-star Ruby Keeler and later appearing in the touring production starring Don Ameche and Evelyn Keyes.
According to a 1915 article in The Day Book, the young Donnelly was forced to leave Sacred Heart Convent in New Jersey because she repeatedly broke into laughter at inappropriate times.
Donnelly began her stage career at the age of 17 in The Quaker Girl. Actress Rose Stahl took the teen under her wing and, after giving her training and a year's experience in the chorus, placed the then 18-year-old in the play Maggie Pepper. Her Broadway debut brought her to the attention of George M. Cohan, who proceeded to cast her in numerous comic-relief roles in such musicals as Going Up (1917).