Born in New York City, Zambello lived in Europe when she was a child, learning to speak French, Italian, German and Russian.
She debuted in Europe at Teatro La Fenice in Venice with Beatrice di Tenda in 1987 and has since staged new productions at major theaters, festivals and opera houses around the world.
Zambello developed and directed the world premiere of Christopher Theofanidis' Heart of a Soldier for the San Francisco Opera, where she was artistic advisor from 2006 to 2011.
Theater projects have included Show Boat in London at the Royal Albert Hall as well as for the Lyric Opera of Chicago and San Francisco Opera; a new musical, Rebecca, for Vienna's Raimund Theater, Stuttgart's Palladium Theater [de] (presented by Stage Entertainment), and in St. Gallen, Switzerland; Tibet Through the Red Box, a new play by David Henry Hwang for the Seattle Children's Theatre; The Little Prince with Oscar-winning composer Rachel Portman; Napoleon in the West End; The Little Mermaid for Disney on Broadway; the musical of The Little House on the Prairie and The Master Butchers at the Guthrie Theater, and Aladdin in Disneyland.
Works on DVD include War and Peace, Carmen, The Little Prince, Street Scene, Show Boat and Porgy and Bess.