After a brief unsuccessful marriage to Auguste-Armand Vestris, a ballet dancer, Mme Vestris first appeared in Italian opera in 1815 and enjoyed immediate success in London and in Paris, where she played with F.-J. Talma. Because of her low voice and vivacious manner she was a particular favourite in such breeches parts as Cherubino in The Marriage of Figaro and in Giovanni in London. In 1831 she became lessee of the Olympic Theatre and began presenting the burlesques and extravaganzas for which that house became known. Her insistence on real props and historically accurate costuming set new standards in stage design. She was also the first to use the box set, a ceilinged room with one wall removed. After 1838 with her second husband, the actor Charles James Mathews, she managed the Lyceum and Covent Garden Theatres until 1854.

A biography, Madame Vestris and the London Stage, was published in 1974.