Effinger 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 with the trilogy of Marîd Audran novels set in a 22nd-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 version of the French Quarter of New Orleans. The three published novels were When Gravity Fails (1987), A Fire in the Sun (1989), and The Exile Kiss (1991); Effinger also contributed to the computer game Circuit's Edge (1990), set between the first two books. He began a fourth Budayeen novel, Word of Night, but completed only the first two chapters. Those two chapters were reprinted in the anthology Budayeen Nights (2003) which has all of Effinger's short material from the Marîd Audran setting.
His novelette "Schrödinger's Kitten" (1988) received both the Hugo and the Nebula Award, as well as the Japanese Seiun Award. A collection of his stories was published posthumously in 2005, entitled George Alec Effinger Live! From Planet Earth; includes the complete stories Effinger wrote under the pseudonym "O. Niemand" and many of Effinger's best-known stories. Each O. Niemand story is a pastiche in the voice of a different major American writer (Flannery O'Connor, Damon Runyon, Mark Twain, etc.), all set on the asteroid city of Springfield. "Niemand" is from the German word for "nobody", and the initial O was intended by Effinger as a visual pun for Zero, and possibly also as a reference to the author O. Henry.
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.
He made brief forays into writing comic books in the mid-1970s and again in the mid-1980s, including the first issue of a series of his own creation entitled Neil and Buzz in Space & Time, about two fictional astronauts who travel to the edge of the universe to find it contains nothing but an ocean planet with a replica of a small New Jersey town on its only island. The first issue was the only issue, and the story ended on a cliffhanger. It was released by Fantagraphics. He also wrote a story based in the Zork universe.
Effinger was known to close friends as "Piglet", a nickname from his youth which he later came to dislike.
Throughout his life, Effinger suffered from health problems. These resulted in enormous medical bills which he was unable to pay, resulting in a declaration of bankruptcy. Because Louisiana's system of law descends from the Napoleonic Code rather than English Common Law, the possibility existed that copyrights to Effinger's works and characters might revert to his creditors, in this case the hospital. However, no representative of the hospital showed up at the bankruptcy hearing, and Effinger regained the rights to all his intellectual property.
Effinger suffered a hearing loss of about 70% due to childhood infections, only helped about the last 10 years of his life by hearing aids. He did not drive most of his life, and only got a driver's license at about age 39 for check-cashing purposes.
Effinger met his first wife Diana in the 1960s. He was married from the mid-1970s to the mid-1980s to artist Beverly K. Effinger, and from 1998 to 2000 to fellow science fiction author Barbara Hambly. He died in New Orleans, Louisiana.
Note: The titles of the first two books of the Marîd Audran series are both taken from Bob Dylan lyrics. "When Gravity Fails" is from the song "Just Like Tom Thumb's Blues" and "A Fire in the Sun" from "It's All Over Now, Baby Blue". Permission was denied to use a Dylan quote again for the third book's title, so Effinger chose instead a public domain quote from Shakespeare.