Her best-known roles are as Audrey in the original stage play and film adaptation of Little Shop of Horrors, and as Vivian Charles in the ABC series Pushing Daisies.

[6] Greene's career began as a nightclub singer in clubs such as The Brothers and Sisters, Continental Baths, Grand Finale, and Reno Sweeney's.

[10] Continuing her work with Papp's New York Shakespeare Festival, Greene next played the role of Jenny in The Three Penny Opera (1976) at the Vivian Beaumont Theater in Lincoln Center, for which she was nominated for a 1977 Tony Award, Featured Actress In A Musical.

[11] In addition to a number of other productions with the New York Shakespeare Festival and numerous other companies, Greene formed a close working relationship with the WPA Theatre, where she met Howard Ashman and Alan Menken.

Their close, long-lasting friendship led to her landing the role of Audrey in Little Shop of Horrors, which she reprised in the film version opposite Rick Moranis.

Other work includes the role of Vivian Charles on the television series Pushing Daisies (2007)[18] and the voice of Dolly Gopher in the animated Out of Jimmy's Head.

[19] In July and August 2009, Greene starred as Miss Adelaide in a concert version of the musical Guys and Dolls, which had a 3-day engagement at the Hollywood Bowl in Los Angeles, California.

Her co-stars included Scott Bakula as Nathan Detroit, Brian Stokes Mitchell as Sky Masterson, and Jessica Biel as Sarah Brown.