Making her stage debut in London in 1914 as a sentimental-ballad singer, Lillie proved her comic genius in a series of revues produced by André Charlot during World War I. In 1924 she made her first New York City appearance in a revue, establishing her reputation as an international celebrity. She appeared in at least one comedy revue a year from 1914 to 1939. After her film debut in the silent Exit Smiling (1926), she made other occasional screen appearances. After World War II she appeared in the revue Inside U.S.A. (1948–50) and toured in a one-woman show entitled An Evening with Beatrice Lillie (1952 and revised later productions). Her last stage performances were in Auntie Mame (1958, London) and High Spirits (1964, New York City), the musical version of Noël Coward's Blithe Spirit.

In 1920 she married Sir Robert Peel (d. 1934), who succeeded as 5th Baronet Peel in 1925. Her autobiography, Every Other Inch a Lady, was published in 1973.