He is best known for the George Miles Cycle, a series of five semi-autobiographical novels published between 1989 and 2000 and described by Tony O'Neill "as intense a dissection of human relationships and obsession that modern literature has ever attempted.

[10] Cooper started Little Caesar Magazine in 1976; the punk zine, which ran for 12 issues between 1976 and 1982, featured multimedia contributions from Andy Warhol, David Wojnarowicz, Debbie Harry, Bob Flanagan, and Toby Ross.

[20][3] Cooper returned to Los Angeles in 1990 and continued collaborating with other artists, including composer John Zorn, painter Lari Pittman, sculptors Jason Meadows and Nayland Blake, and others.

[10][8][21][22] He also started the Little House on the Bowery curated imprint, which included works from Travis Jeppesen, Richard Hell, James Greer, Trinie Dalton, Derek McCormack, and others, under the independent publisher Akashic Books.

[33][34] Since living in France, Cooper has published a number of novels, had a cameo in Christophe Honoré's Homme au Bain,[35] released a book/CD collaboration with Gisèle Vienne and Peter Rehberg,[36] reissued the graphic novel Horror Hospital Unplugged he released with Keith Mayerson in 1997,[37] and curated part of the 2012 Un Nouveau Festival with Gisèle Vienne.

[41] In mid-2016, Cooper engaged in a two-month standoff with Google after it deleted his blog[42] and Gmail accounts without warning, due to what the company described as unspecified violations of their terms of use policy.

[43] Cooper's plight attracted media attention,[44][45] including from The New York Times,[46] The New Yorker,[47] The Guardian,[48] Le Figaro,[49] and Die Welt.

[51] Cooper's work has been acknowledged as an influence on a number of writers, including Travis Jeppesen, Kay Gabriel, Tony O'Neill, Jackie Ess, Noah Cicero, Shiv Kotecha, Jon Lindsey, Dominic Lyne[52] and Poppy Z.

[54] American indie rock band Deerhunter, and grindcore act Pig Destroyer have both cited Dennis Cooper as a lyrical influence.

[55] Cooper has also influenced a number of artists such as Ryan Trecartin, Jonathan Mayhew, Lizz Brady, Chris Kelso, Daniel Portland, Jared Pappas-Kelley, Ken Baumann, Blair Mastbaum, which he has included in exhibitions such as the Weaklings or who he has showcased over the years.

— 3:AM Magazine, November 2001, "American Psycho: An Interview With Dennis Cooper" by Stephen Lucas[61] "George in Closer, whose room is full of Disney figures, himself becomes the toy of two forty-year-old men obsessed with the beauty of pain and suffering.

— VPRO Television; article in Dutch[62] In 2021, Cooper published I Wished, a sort of coda of the George Miles Cycle, through Soho Press.