Hull had her first major stage success in George Kelly's Pulitzer-winning "Craig's Wife" in 1926. Kelly wrote a role especially for her in his next play "Daisy Mayme" which also was staged in 1926. She continued working in New York theater throughout the 1920s. In the 30s, Hull scored in three great Broadway hits, as a batty matriarch in "You Can't Take It With You" (1936), as an agreeably homicidal aunt in "Arsenic and Old Lace" (1941), and in "Harvey" (1944). The plays all had long runs, and took up ten years of Hull's career.
Hull only made five films, beginning with two 1932 Fox features, "After Tomorrow" (recreating her stage role) and "The Careless Lady". She missed out on recreating her "You Can't Take It With You" role in 1938, as she was still onstage with the show (Spring Byington filled in onscreen). But Hull and Jean Adair did play the Brewster sisters in the 1944 film "Arsenic and Old Lace", and Hull was in the screen "Harvey" as well. It is for that role that she won her 1950 Oscar as Best Supporting Actress. "Variety" said that Hull, as "the slightly balmy aunt who wants to have Elwood committed, is immense, socking the comedy for every bit of its worth".
Hull made only one further film, the 1951 "The Lady from Texas", and appeared in the CBS-TV version of "Arsenic and Old Lace" in 1949 (with Ruth McDevitt as her sister). Moving to the Bronx, Hull had been retired for some years before her death in 1957.