[6] After a period outside New York, Wojnarowicz returned in the late 1970s and emerged as one of the most prominent and prolific members of an avant-garde wing that used mixed media as well as graffiti and street art.

Wojnarowicz completed a 1977–1979 photographic series on Arthur Rimbaud, did stencil work and collaborated with the band 3 Teens Kill 4, which released the independent EP No Motive in 1982.

He made autonomous super-8 films such as Heroin and Beautiful People with bandmate Jesse Hultberg, and collaborated with filmmakers Richard Kern and Tommy Turner of the Cinema of Transgression.

Wojnarowicz was also connected to other prolific artists of the time, appearing in or collaborating on works with Nan Goldin, Peter Hujar, Luis Frangella, Karen Finley, Kiki Smith, James Romberger, Marguerite Van Cook, Ben Neill, Marion Scemama,[7] and Phil Zwickler.

Hujar's death moved Wojnarowicz to create much more explicit activism and political content, notably about the social and legal injustices related to the government response to the AIDS epidemic.

[1] He collaborated with video artist Tom Rubnitz on the short film Listen to This (1992), a critique of the Reagan and Bush administrations' homophobic responses and failure to address the crisis.

In the 1990s, he sued and obtained an injunction against Donald Wildmon and the American Family Association on the grounds that Wojnarowicz's work had been copied and distorted in violation of the New York Artists' Authorship Rights Act.

Knives opens with an essay about his homeless years: a boy in glasses selling his skinny body to the pedophiles and creeps who hung around Times Square.

The heart of Knives is the title essay, which deals with the sickness and death of Hujar, Wojnarowicz's lover, best friend and mentor, "my brother, my father, my emotional link to the world".

[12] In 1989, Wojnarowicz appeared in Rosa von Praunheim's widely acclaimed film Silence = Death about gay artists in New York City fighting for the rights of AIDS sufferers.

[13] In November 2010, after consultation with National Portrait Gallery director Martin Sullivan and co-curator David C. Ward but not co-curator Jonathan David Katz,[14] Smithsonian Institution Secretary G. Wayne Clough removed an edited version of footage used in Wojnarowicz's short silent film A Fire in My Belly from the exhibit "Hide/Seek: Difference and Desire in American Portraiture" at the National Portrait Gallery in response to complaints from the Catholic League, U.S. House Minority Leader John Boehner, Representative Eric Cantor and the possibility of reduced federal funding for the Smithsonian.

On October 11, 1992, activist David Robinson received wide media attention when he dumped the ashes of his partner, Warren Krause, on the grounds of the White House as a protest against President George H. W. Bush's inaction in fighting AIDS.

[43] On September 13, 2021, at the Met Gala in New York City the Canadian actor Dan Levy wore an outfit by designer Jonathan Anderson for Loewe which prominently featured an adapted version of Wojnarowicz's artwork F--- You F----- F----- depicting two men kissing while shaped as maps, with the support of the visual artist's estate.