He was a part of the Clarion class of 1970 and had three stories in the first Clarion anthology. His first published story was "The Eight-Thirty to Nine Slot" in Fantastic in 1971. During his early period, he also published under a variety of pseudonyms.
His first novel, What Entropy Means to Me (1972), was nominated for the Nebula Award. He achieved his greatest success, perhaps, with the trilogy of Marid Audran novels set in a 21st century Middle East, with cybernetic implants and modules allowing individuals to change their personalities or bodies. The novels are in fact set in a thinly veiled New Orleans, telling the fictionalized stories of the transvestites and other people Effinger knew in the slums of that city. The three published novels were When Gravity Fails (1987), A Fire in the Sun (1989), and The Exile Kiss (1991). He apparently wrote a fourth book. However, legal issues prevented its publication.
His novelette, "Schrödinger's Kitten" (1988), received both the Hugo and the Nebula Award.
Other stories he wrote were the series of Maureen (Muffy) Birnbaum parodies, which placed a preppy into a variety of science fictional, fantasy, and horror scenarios.
Throughout his life, Effinger suffered from health problems. These resulted in enormous medical bills which he was unable to pay. A lawsuit by the hospital tied up the rights to all of his books and characters, causing a dearth of Effinger material. Eventually the suit was dropped, and Effinger regained the rights to all his intellectual property.
Effinger was married, mid-1970s to mid-1980s, to artist Beverly K. Effinger, and for a few years shortly before his death to fellow science fiction author Barbara Hambly.
Effinger died in New Orleans, Louisiana.