As a musician, she leads the band The Voluptuous Horror of Karen Black, who are inspired by glam, punk and shock rock.

[5] Hans Ulrich Obrist described Pfahler as a 'pioneer' of the Cinema of Transgression and of performance art and 'pioneering' as a musician and actress, and has called her interdisciplinary practice a 'Gesamtkunstwerk.

[9] With best friend and collaborator Gordon Kurtti, Pfahler created live performances for Life Café, 8BC and Danceteria.

In 1984 Pfhaler and Kurtti organized The Extremist Show at ABC No Rio in the Lower East Side – featuring many of New York's sub-culture artists and groups including P.O.O.L., Samoa Moriki and his punk rock band BALLS, The Church of the Little Green Man, and the Cinema of Transgression featuring the films of Nick Zedd, Lydia Lunch and Richard Kern, Borbetomagus and Red Dog Magazine.

Other performances developed at this time included walking on bowling balls and cracking paint-filled eggs on her vulva.

[13] Pfahler sang backup on the song "Shoot, Knife, Strangle, Beat and Crucify" on the album Brutality and Bloodshed for All of GG Allin and the Murder Junkies.

[14] In Richard Kern's Sewing Circle (1992), Pfhaler had her vagina sewn shut by artist Lisa Resurreccion while only wearing a "Young Republicans" t-shirt, back stockings and garters.

[16] In January 2007, Pfahler, with Julie Atlas Muz, curated a mixed-media art exhibition titled Womanizer at Deitch Projects.

[18] As part of the 2008 Whitney Biennial and with support from the Art Production Fund, Pfahler and Voluptuous Horror gave a performance in the Park Avenue Armory's Drill Hall on March 14, 2008.

She stars as 'Sister Kembra' in Bruce LaBruce's The Misandrists (2017) and was interviewed as part of the documentary The Advocate for Fagdom by Angélique Bosio about the queercore filmmaker.

Pfahler founded the art movements and conceptual philosophies of Availabilism (sometimes written as 'availabism'),[27][11] using what is closest at hand ("available") as both the inspiration for her work and the medium of her expression.

[6] In 2011, Pfahler co-created Future Feminism alongside Anohni, Bianca and Sierra Casady (of CocoRosie), and Johanna Constantine.

[34] The group of five women stated that their aim with the project is a "a "call to arms to reorganize ourselves as a species and affirm archetypally feminine values.

[34] The show was re-staged at the 'O' Space gallery in Aarhus, Denmark as part of the 2017 European Capital of Culture and featured a series of debates, presentations, performances and workshops.

[36][37] The group is credited with popularising the slogan 'the future is female' from 2014 onwards, which was then marketed by t-shirt companies and used by Hillary Clinton in a 2017 speech.