Gordon attended Phillips Academy, but left without graduating in 1952. Later, in 1959, he graduated with a bachelor's degree in English with honors from the University of Arizona, where he met his first wife, Loretta Frances Fokes. They married in November 1956 and together had 3 children.

Following Lish's graduation, the family moved to San Francisco; here Lish had a year of graduate study at San Francisco State University in 1960. In Early 1961, Candido Santogrossi and Lish founded a new Pacific Coast avant-garde literary journal, The Chrysalis Review.

He is a father of four (Jennifer, Rebecca, Ethan, and Atticus), and a grandfather of six (Anne, and Carla, children of Jennifer; Pearl and Ezra, children of Rebecca; and Nina and Isaac, children of Ethan).

As founder and editor of Genesis West

In 1960, the Lish family moved to Burlingame, California, where they founded the avant-garde literary magazine Genesis West, which ran between 1961 and 1965. Genesis West was published in seven volumes by The Chrysalis West Foundation. While working on Genesis West, their house and magazine became a focus point, and celebrated and introduced such authors and poets as Neal Cassady, Ken Kesey, Jack Kerouac, Allen Ginsberg, Jack Gilbert, and Herbert Gold.

The Lish family often hosted the likes of Ken Kesey and Neal Cassady in their Burlingame home. The Merry Pranksters' wildly painted school bus, 'Further,' driven by Neal Cassady, was often parked in front of their home. Neal Cassady makes note of his time spent at the Lish home on page 151 of his only self-authored book, The First Third. Carolyn Cassady makes note of the Lish home on page 387 of Off The Road.

In 1963, Lish became director of linguistic studies at Behavioral Research Laboratories in Menlo Park, California. There, in 1964, he produced English Grammar, a text for educators; Why Work, a book of interviews; New Sounds in American Fiction, a set of recorded dramatic readings of short stories; and A Man's Work, an information motivation sound system in vocational guidance. It consisted of over 50 translucent albums.

While in Menlo Park, one of Lish's friends was Raymond Carver, who was editing educational materials in an office across the street from Lish's office. Lish edited a number of stories which wound up as Carver's first national magazine publications.

Editor at Esquire magazine

Lish and his second wife moved to New York City, where Lish served as the fiction editor at Esquire from 1969 to 1976; here he became known as "Captain Fiction" for the number of authors whose careers he assisted. Lish published numerous Bart Midwood and Raymond Carver stories in Esquire, and championed the work of Richard Ford; he also promoted the work of such writers as Cynthia Ozick, Don DeLillo, Reynolds Price, T. Coraghessan Boyle, Raymond Kennedy and Barry Hannah.

While at Esquire, Lish edited the collections The Secret Life of Our Times and All Our Secrets Are the Same, which contained pieces by a number of prominent authors, from Vladimir Nabokov to Milan Kundera.

In February 1977, Esquire published "For Rupert - with no promises" as an unsigned work of fiction: this was the first time it had published a work without identifying the author. Readers speculated that it was the work of J. D. Salinger, but it was in fact a clever parody by Lish, who is quoted as saying, "I tried to borrow Salinger's voice and the psychological circumstances of his life, as I imagine them to be now. And I tried to use those things to elaborate on certain circumstances and events in his fiction to deepen them and add complexity." The Wall Street Journal February 25, 1977

Editor at Alfred A. Knopf

Lish left Esquire in 1977 to become a senior editor with the publishing firm of Alfred A. Knopf; he remained here until 1995 and continued to champion new fiction, publishing works by Cynthia Ozick, David Leavitt, Amy Hempel, Noy Holland, Lynne Tillman, William Ferguson, Barry Hannah, Harold Brodkey, Raymond Carver and Joy Williams. After Lish retired from both teaching and publishing, some of his students continued to make noted contributions to American letters, the National Book Award was won in 2004 by Lily Tuck for her novel The News From Paraguay. In the same year Christine Schutt's Florida was a finalist, and Dana Spiotta was a finalist for the award in 2006 for Eat The Document. Other former students whose writing has met with praise include Diane Williams, Dawn Raffel, Victoria Redel, Gary Lutz, Ben Marcus, Sam Lipsyte, Will Eno, and Bahamian writer Garth Buckner, whose The Origins of Solitude met with some critical acclaim.

Lish also continued teaching creative writing, inspiring writers including Amy Hempel (who dedicated her collection Reasons to Live to him).

During his time at Knopf, Lish published several volumes of his own fiction:

• Dear Mr. Capote, his first novel.
• What I Know so far, a collection of short stories, was published in 1984 and included "For Rupert...with no Promises.", and the O. Henry Award-winning "For Jeromé...with Love and Kisses," a parody of J. D. Salinger's story, "For Esmé...with Love and Squalor."
• Peru, was published in 1986.

In 1987, Lish founded and edited the avant garde literary magazine, The Quarterly, which showcases the works of contemporary authors. Six volumes were published by the summer of 1988, and such authors were introduced as J. E. Pitts, Jane Smiley, Mark Richard, and Jennifer Allen. By the time the Quarterly ended in 1995, it had published 31 volumes.

Lish continued to write fiction, including Mourner at the door in 1988, Extravaganza in 1989, My Romance in 1991, and Zimzum in 1993. For the June 1991 issue of Vanity Fair, James Wolcott wrote a profile on Gordon Lish and Don DeLillo called "The Sunshine Boys."

He was the recipient of a Guggenheim Fellowship in 1984; that same year, his wife Barbara died.

On August 9, 1998, The New York Times Magazine published an article by D.T. Max about claims that the late Raymond Carver's early short stories were more or less ghost-written by Lish, his editor. Other writers associated with Carver, such as Tobias Wolff and Tess Gallagher (Carver's wife at the time of his death) have steadfastly denied such claims, although Carver wrote Lish: “If I have any standing or reputation or credibility in the world, I owe it to you.” In December 2007 The New Yorker magazine published an earlier and much longer draft of Carver's story "What We Talk About When We Talk About Love" under Carver's title, "Beginners." The magazine published Lish's extensive edits of the story on its web site for comparison. In May 2010 Giles Harvey wrote an article in the New York Review of Books reviewing Carver's work, and made the observation "The publication of 'Beginners' has not done Carver any favors. Rather, it has inadvertently pointed up the editorial genius of Gordon Lish."

Lish has placed all his papers and manuscripts at the Lilly Library of Indiana University. He was named one of the 200 major writers of our time by the French periodical Le Nouvel Observateur.

For three years in the early 1960s, Lish taught as an English teacher at Mills High School, Millbrae, California. His high school teaching career ended when school administrators declined to give him tenure. Donovan Bess, writing in The Nation Magazine, wrote that "essentially, Lish is accused: of reciting the Pledge of Allegiance to the Flag too speedily (time: 8.7 seconds); of “teaching on Cloud Seven” (two clouds too high); of flouting the system by, for example; making the kids give the answers’ of being “a screwball”; of wearing a hat indoors; of founding a “beatnik” literary magazine, called Genesis West; of using the word “shit” in a short story; of being unpredictable and moody-looking; of sponsoring avant-garde student poetry (at Mills, poetry that does not rhyme is avant-garde)”. Several students and adults testified on his behalf at the hearing. The full story is detailed in “The Man Who Taught Too Well" By Donovan Bess, The Nation Magazine, June 15, 1963, pages 507-516.

In addition to his career in literary publishing, Lish has conducted writing seminars in New York City and served as a lecturer at Yale University, New York University and Columbia University.

Don DeLillo acknowledged Lish's influence as a teacher and friend in dedicating his book Mao II to Lish. Lish dedicated his books My Romance, Mourner at the Door and Epigraph to Don DeLillo. Lish also wrote an afterword to the publication of Don DeLillo's first play, The Engineer of Moonlight, in which he attacks those who would call DeLillo's vision bleak. "Where we are and where we are going is where DeLillo is. He is our least nostalgic writer of large importance."

He is an honorary doctor of letters from State University of New York awarded in 1994. He retired from teaching fiction writing in 1997 but came out of retirement to teach during the summers of 2009 and 2010 at the Center for Fiction in Manhattan.

David Leavitt's novel Martin Bauman; or, A Sure Thing documents the narrator's experiences under the tutelage of Gordon Lish. In the novel, Lish is the basis for the character of Stanley Flint, an enigmatic writing teacher. T. Gertler's novel, Elbowing the Seducer, has a character who is a book editor and womanizer who is apparently based on Lish. It is unknown who Gertler really is -- this writer only published on story in Esquire and one novel. In Barry Hannah's short novel, Ray, there is a character called Captain Gordon who is based on Lish, and Lish appears as himself in Hannah's Boomerang.