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 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, telling the fictionalized stories of the transvestites and other people Effinger knew in the bars of that city. The three published novels were When Gravity Fails (1987), A Fire in the Sun (1989), and The Exile Kiss (1991). 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 stories was published posthumously in 2005 entitled George Alec Effinger Live! From Planet Earth and 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'Conner, 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 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.

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.

He 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 drivers 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 for a few years shortly before his death to fellow science fiction author Barbara Hambly.

Effinger died in New Orleans, Louisiana.

Planet of the Apes Television series adaptations

• Man the Fugitive (1974)
• Escape to Tomorrow (1975)
• Journey Into Terror (1975)
• Lord of the Apes (1976)

Nick of Time series

• The Nick of Time (1985)
• The Bird of Time (1986)

Marîd Audran series

• When Gravity Fails (1987)
• A Fire in the Sun (1989)
• The Exile Kiss (1991)
• The Audran Sequence (omnibus)

Free standing novels

• What Entropy Means to Me (1972)
• Relatives (1973)
• Nightmare Blue (1975) (with Gardner Dozois)
• Felicia (1976)
• Those Gentle Voices: A Promethean Romance of the Spaceways (1976)
• Death in Florence (1978) (aka Utopia 3)
• Heroics (1979)
• The Wolves of Memory (1981)
• Shadow Money (1988)
• The Red Tape War (1990) (with Mike Resnick and Jack L. Chalker)
• The Zork Chronicles (1990)
• Look Away (1990) (novella)
• Shrodinger's Kitten (1992)
• Trinity: Hope Sacrifice Unity
• The League of Dragons: A Castle Falkenstein Novel (1998)
• The Bird of Time (2004)

Collections

• Mixed Feelings (1974)
• Irrational Numbers (1976)
• Dirty Tricks (1978)
• Idle Pleasures (1983) (science fiction sports stories)
• Author's Choice Monthly Issue 1: The Old Funny Stuff (1989)
• Maureen Birnbaum, Barbarian Swordsperson (1993)
• Budayeen Nights (stories set in the world of the Marîd Audran series, 2003)
• George Alec Effinger Live! From Planet Earth (stories selected and introduced by GAE's friends and fellow writers and editors, 2005)
• A Thousand Deaths (2007) (contains the novel The Wolves of Memory plus seven additional Sandor Courane stories, six of which are previously uncollected)

Short stories

• "The Home Front" (1996)
• " The Last Full Measure "

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.

He was left-handed.