On 17 September 1883, May Robson became an actress in Hoop of Gold at the Brooklyn Grand Opera House stage. Her name was incorrectly spelled “Robson” in the billing, which she used from that point forward “for good luck”. Over the next several decades, she flourished on the stage as a comedienne and character actress. Her success was partly due to her affiliation with powerful manager and producer Charles Frohman and the Theatrical Syndicate. She established her own touring theatrical company by 1911. She appeared as herself in a cameo in the 1915 silent film, How Molly Made Good. May Robson starred in the 1916 silent film A Night Out, an adaptation of the play she co-wrote, The Three Lights. In 1927 Robson attended Edinburgh University, then went to Hollywood where she had a successful film career as a senior aged woman. Among her starring roles was in The She-Wolf (1931) as a miserly millionaire businesswoman based on the real-life miser Hetty Green. May Robson also starred in the final segment of the anthology film If I Had a Million (1932) as a rest home resident who gets a new lease on life when she is given a $1,000,000 check by a dying business tycoon. She played the Queen of Hearts in Alice in Wonderland (1933), Countess Vronsky in Anna Karenina (1936), Aunt Elizabeth in Bringing Up Baby (1938), Aunt Polly in The Adventures of Tom Sawyer (1938), and a sharp-tongued Granny in A Star Is Born (1937). Robson was top-billed as late as 1940, starring in Granny Get Your Gun at age 82. Her last film was 1942’s Joan of Paris.

In 1933, May Robson was nominated for an Academy Award at age 75 in the Best Actress category for Lady for a Day but lost to Katharine Hepburn; the two actresses both appeared in the Hepburn-Grant classic film, Bringing Up Baby. Robson was the first Australian-born person to be nominated for an acting Oscar, and, for many years, she held the record as the oldest performer nominated for an Oscar. May Robson died in her Beverly Hills, California home at age 84. In its obituary of Robson, the Nevada State Journal stated that Robson died of “a combination of ailments, aggravated by neuritis and advanced age.” Her remains were cremated and buried at the Flushing Cemetery in Queens, New York, next to her second husband, Augustus Brown. The New York Times obituary for Robson called her the “dowager queen of the American screen and stage”.