The daughter of jazz pianist Robert DeLaria, she actually began her career as a jazz singer at age 16. By 1982, DeLaria had relocated to San Francisco and was persuaded to try her hand at standup. Instead of her own name, she first performed under the moniker 'the F--ing Dyke' and proved to be a hit with audiences. After a decade of playing clubs and college campuses, DeLaria made that appearance on Hall's show and her profile rose almost overnight. She debuted her club act, a mix of singing and comedy and performed at that year's gay and lesbian March on Washington. In 1994, she began acting the recurring role of a police detective in episodes of ABC's "Matlock". Her first film role came in 1996 in a bit part of a woman who makes a pass at Goldie Hawn in a lesbian bar in "The First Wives Club".

1997 proved a banner year for DeLaria when New York Shakespeare Festival artistic director George C Wolfe tapped her to portray the tough talking cabbie Hildy in his Central Park revival of "On the Town". While there were many who expressed disbelief at her casting, she eventually wowed critics and audiences. Those who knew her as "that lesbian comic" were shocked at her Ethel Merman-like vocal abilities and she once and for all proved she was capable of playing any role. Although the production was eventually recreated the following year indoors, it was not a success and DeLaria's much expected Tony nomination failed to materialize.

Undaunted, she soon found herself in demand and accepted a variety of roles that confounded stereotype and displayed her versatility. She crossed genders to play Marryin' Sam in a concert staging of "Li'l Abner" in 1998 and again played a taxi driver, this time chauffeuring Quentin Crisp in the indie feature "Homo Heights" (1998). DeLaria gave a nicely modulated performance as a lesbian bar owner who helps a teenager struggling with his sexual orientation in "Edge of Seventeen" (1999). She also returned to the stage in Paul Rudnick's spin on the bible "The Most Fabulous Story Ever Told", toured as the prison matron Mama Morton in "Chicago" and took on a recurring role as an eccentric psychic on the ABC daytime drama "One Life to Live". DeLaria even tackled Shakespeare playing the shepherdess Audrey in a Williamstown Theatre Festival production of "As You Like It" headlined by Oscar-winner Gwyneth Paltrow. Although her recurring role as a receptionist in a police station on UPN's "The Beat" disappeared from the airwaves rather quickly, DeLaria quickly switched gears again and accepted the roles of Eddie and Dr Scott (played by Meat Loaf in the original production) in the Broadway revival of "The Rocky Horror Show". Once again, she managed to wow audiences and critics with her charismatic stage presence and terrific vocal prowess.