Gary Indiana's fiction is directly contemporary. He is known for his loose trilogy of books based on notorious criminals in the media spotlight. While Three Month Fever is presented as an account of Andrew Cunanan, the man who murdered Gianni Versace, it uses fictional recreations of undocumented conversations and events to explore contemporary American obsession with celebrity and fame. More obviously a novel, Resentment seems nevertheless to be an account, or perhaps a speculative exploration, of the case of California brothers Lyle and Erik Menendez, convicted of the murder of their parents, though names and other details have been changed. This same method of a fictionalized account of real events can be found in Depraved Indifference, in which Indiana makes use of the case of Sante and Kenneth Kimes, mother-and-son con artists convicted of murdering heiress Irene Silverman (though again, names and details are changed). Indiana uses this material to explore matters such as masculinity, taboo, sexuality, and violence.

Indiana has also based multiple novels on fictionalized events from his own life and those of his associates and contemporaries. Gone Tomorrow, for example, mines his history as a film actor, particularly his work with German director Dieter Schidor and others in Rainer Werner Fassbinder's circle. Years later, Indiana returned to the raw material of his own life for Do Everything in the Dark, in which characters from earlier novels such as Horse Crazy and Gone Tomorrow return in a later, more melancholic stage of life.

In 2009, New York-based independent publishers Two Dollar Radio published Indiana's most recent novel, The Shanghai Gesture. (The Shanghai Gesture is also the name of a 1941 film by Josef von Sternberg.)

Indiana's plays include "Roy Cohn/Jack Smith", performed by Ron Vawter; Indiana wrote the half depicting a speech by Roy Cohn, while the other part was based on a performance by the underground filmmaker Jack Smith.

Indiana's journalism has appeared in The Village Voice, the Los Angeles Times Book Review, New York Magazine and the London Review of Books, among others.

In the early 1980s, Indiana established his name in art writing, despite having no formal education in art theory or practice. After writing several extended essays on, primarily, mid-century art for Art in America, Indiana joined the New York alternative weekly The Village Voice as art critic in 1985. This was a particularly influential position, given that the Voice was then one of only two New York newspapers that reviewed exhibitions still hanging. It was at the Voice that Indiana's journalistic style...an intelligent blend of dark wit, penetrative observation and uncompromising honesty...came into its own. Clear prose (notwithstanding a notable vocabulary) and a particular interest in the social and commercial context of art set his work apart from much art writing in the period. The excesses and political pressure of the booming 1980s art market led him to become unhappy in the position, however, and he left the paper in 1988.

He was largely to forgo art criticism during much of the following period, concentrating instead on his literary work...his primary interest. But he has subsequently returned to art writing as a contributor to Artforum and to monographs on, among others, Cameron Jamie, Roberto Juarez and Nancy Chunn. Samples of his work for Art in America, the Voice and Artforum, among other publications from this period, have been collected in the anthology Let It Bleed: Essays 1985—1995. A later collection, Utopia's Debris, collects further critical pieces.

Today, Indiana writes on a wide variety of cultural phenomena, covering topics from art, literature and film to politics and the media. He has authored a study of Pier Paolo Pasolini's Salò for the British Film Institute, and in 2005 published The Schwarzenegger Syndrome: Politics and Celebrity in the Age of Contempt, an account of Arnold Schwarzenegger's election to the governorship of California and its broader cultural implications. Basic Books is soon to publish Andy Warhol and the Can That Sold the World, Indiana's exploration of the iconic Andy Warhol exhibition of 1962, 32 Soup Cans. Semiotexte/MIT Press is also slated to release a collection of Indiana's non-fiction work, Last Seen Entering the Biltmore: Selected Writings 1976-1994.

Indiana has acted in a number of films, several of them German. His novel Gone Tomorrow reflects his experiences on the set, particularly his time working on Dieter Schidor's 1985 film Cold in Columbia.

Two films by Indiana have been in post-production for some time: Pariah (about Ulrike Meinhof) and Soap (based on the Francis Ponge poem).