Ellen Greene's journey in the entertainment industry began with her performances as a nightclub singer in various New York City clubs and her appearances on the stages of New York City theater. Her big break came when her friend and mentor, filmmaker Paul Mazursky, cast her in her first motion picture, Next Stop, Greenwich Village, in 1976. Greene was awarded the role of Sarah, opposite Lenny Baker, and this marked the beginning of her successful career in film and television.
Four years later, Greene originated the iconic role of Audrey in Howard Ashman's Off-Broadway play, The Little Shop of Horrors, in 1982. Her portrayal of the lovably ditzy, golden-hearted, sweetest masochist in musical-comedy history earned her widespread recognition and acclaim. Greene reprised her role in Frank Oz's film adaptation, Little Shop of Horrors, in 1986, starring alongside Rick Moranis and Steve Martin. To this day, this remains her most celebrated and talked-about role.
In addition to her work in Little Shop of Horrors, Greene has appeared in a variety of films and television shows. She starred in the American drama film Talk Radio in 1988, playing the part of Ellen opposite Eric Bogosian and Alec Baldwin. Greene has also made guest appearances on popular television series, including Law & Order, The X-Files, Heroes, and The Young and the Restless. Furthermore, she played the role of Lily Charles, an agoraphobic sister, in the ABC fantasy mystery comedy-drama series Pushing Daisies in 2007, alongside Swoosie Kurtz.
In July 2015, Greene reprised her iconic role as Audrey in a two-night revival of Little Shop of Horrors at New York City Center. She starred opposite Jake Gyllenhaal, who replaced Rick Moranis, and the revival received rave reviews. According to The New York Times, Greene's entrance on stage was met with applause similar to that which would greet the resurrection of Maria Callas at the Metropolitan Opera for a beyond-the-grave performance of "Norma."