Lady Bunny began her career alongside Larry Tee and RuPaul as a fixture on the Atlanta gay scene and appeared in a variety of low-budget films with them, including the Starbooty series. In 1984, she moved to New York City, became one of the Club Kids, and in 1985, organized Wigstock, an annual drag queen festival that lasted until 2005. Bunny frequently performs at XL Nightclub with Bianca Del Rio.

In 2003, Lady Bunny made a guest appearance in the Sex and the City episode "Boy, Interrupted", as the emcee at the LGBT prom.

In 2005, she was a roaster on the Comedy Central roast of Pamela Anderson and released her first DVD, Rated X for X-tra Retarded.

Lady Bunny served on the judges' panel on the spinoff show RuPaul's Drag U, which aired on the Logo TV network from 2010 to 2012. Lady Bunny was Dean of Drag and had a role of judge in the first season. In season 2 of RuPaul's Drag U, the Dean of Drag role was expanded into a segment called "Lady Lessons". During the fifth season of RuPaul's Drag Race, contestant Alaska Thunderfuck 5000 impersonated Bunny for the Snatch Game.

Her style of drag performance usually involves lip-synching to a compilation of karaoke versions of popular songs, over which she has recorded her own, sung vocal parodies of the original lyrics. The new lyrics are usually sexually explicit, revolve around food, or both. For instance, her parody of the Gwen Stefani song Hollaback Girl has the lyric: "I shit a banana/a Banana in my ass!" Lady Bunny has released video parodies of "Santa Claus is coming to town" and of "California Gurls" (the latter titled "West Virginia Girls"). Her January, 2011, parody of "Harper Valley PTA", entitled "The Ballad of Sarah Palin", lampooned the American Politician as portrayed by Palin imitator Dorothy Bishop. On July 1, 2013, Lybra Records released remixes of Lady Bunny's collaboration with Wayne Numan, "Take Me Up High" which became her first Billboard Club/Dance hit peaking at #17 in September 2013. In October 2014, she released "Lately" (Remixes) her collaboration with New York City Producers and club DJ's Sean Grasty and DJ Rikky Rivera better known as Groove Addix. Lady Bunny's vocal of "Lately" is already creating a buzz globally in the underground club scene (pre-release) with explicit lyrics: "Pussy this good/Dont wait around for no man-Pussy this good/Dont wait for no nobody." "Lately" will be released on the UK House label Enriched Records which is owned by Rich B, a well known DJ/Artist on London's gay club scene. She also collaborated with New York Producer Ursula 1000 on his track "Blast Off!" from his album Voyeur in 2016.