Anderson early decided upon a career on the stage, and at age 16 she made her debut as Juliet in Louisville, Kentucky. She subsequently toured cities of the South and West and was a popular success, although critical opinion was more reserved, with frequent complaints that she lacked feeling. Her great beauty and remarkable voice won over audiences at her New York City debut in 1877 and at her London debut in 1883.

After a two-year tour of the British Isles, during which she appeared in W.S. Gilbert's Pygmalion and Galatea and Comedy and Tragedy (the latter written especially for her), she returned to New York in As You Like It in 1885. In 1887, again in London, she appeared in her own arrangement of The Winter's Tale, becoming the first actress to play both Hermione and Perdita; the production enjoyed an astounding run of 164 performances. She brought the production to the United States in 1888 and toured with it until she collapsed from nervous exhaustion during a performance in Washington, D.C., in March 1889. The next year she married Antonio Fernando de Navarro and settled with him in Broadway, Worcestershire, England. Her public appearances thereafter were rare.

Anderson published two volumes of autobiography, A Few Memories (1896) and A Few More Memories (1936). She was reputedly the model for the heroine of E.F. Benson (Benson, E.F.)'s popular “Lucia” stories.