John Barth was born in Cambridge, Maryland, and briefly studied "Elementary Theory and Advanced Orchestration" at Juilliard before attending Johns Hopkins University, receiving a B.A. in 1951 and an M.A. in 1952 (for which he wrote a thesis novel, The Shirt of Nessus).

He was a professor at Penn State University from 1953 to 1965. During the "American high Sixties," he moved to teach at SUNY/Buffalo, from 1965 to 1973. In this period he come to know "the remarkable short fiction" of the Argentine Jorge Luis Borges, which inspired him for his collection Lost in the Funhouse.

He later taught at Boston University (visiting professor, 1972—1973), and Johns Hopkins University (1973—1995) before retiring in 1995.

Barth began his career with The Floating Opera and The End of the Road, two short novels that deal wittily with controversial topics, suicide and abortion respectively. They are straightforward tales; as Barth later remarked, he "didn't know they were novels."

The Sot-Weed Factor, Barth's next novel, is an 800-page satirical epic of the colonization of Maryland based on the life of an actual poet, Ebenezer Cooke, who wrote a poem of the same title. The Sot-Weed Factor is what Northrop Frye called an anatomy — a large, loosely structured work, with digressions, distractions, stories within stories, and lists (such as a lengthy exchange of insulting terms by two prostitutes). The fictional Ebenezer Cooke (repeatedly described as "poet and virgin") is a Candide-like innocent who sets out to write a heroic epic, becomes disillusioned and ends up writing a biting satire.

Barth's next novel, Giles Goat-Boy, of comparable size, is a speculative fiction based on the conceit of the university as universe. A boy raised as a goat discovers his humanity and becomes a savior in a story presented as a computer tape given to Barth, who denies that it is his work. In the course of the novel Giles carries out all the tasks prescribed by Joseph Campbell in The Hero with a Thousand Faces. Barth kept a list of the tasks taped to his wall while he was writing the book.

The short story collection Lost in the Funhouse and the novella collection Chimera, the latter for which Barth received the National Book Award, are even more metafictional than their two predecessors, foregrounding the writing process and presenting achievements such as a seven-deep nested quotation. In LETTERS Barth and the characters of his first six books interact.

Barth's fiction continues to maintain a precarious balance between postmodern self-consciousness and wordplay on the one hand, and the sympathetic characterisation and "page-turning" plotting commonly associated with more traditional genres and subgenres of classic and contemporary storytelling.

While writing these books, Barth was also pondering and discussing the theoretical problems of fiction writing.

In 1967 he wrote a highly influential, and for some, controversial, essay which is considered a manifesto of postmodernism, The Literature of Exhaustion (first printed in The Atlantic, 1967). It depicted Literary realism as an “used up” tradition; Barth's description of his own work, which many thought illustrated a core trait of postmodernism, is “novels which imitate the form of a novel, by an author who imitates the role of Author”.

The essay was widely considered to be a statement of "the death of the novel," (compare with Roland Barthes's "The Death of the Author"). Barth has since insisted that he was merely making clear that a particular stage in history was passing, and pointing to possible directions from there. He later (1980) wrote a follow-up essay, "The Literature of Replenishment", to clarify the point.

Fiction

• The Floating Opera (1956)
• The End of the Road (1958)
• The Sot-Weed Factor (1960)
• Giles Goat-Boy, or, The Revised New Syllabus (1966)
• Fiction for Print, Tape, Live Voice (stories) (1968)
• Chimera (three linked novellas) (1972)
• LETTERS (1979)
• A Romance (1982)
• The Tidewater Tales (1987)
• The Last Voyage of Somebody the Sailor (1991)
• A Floating Opera (memoirish novel) (1994)
• On with the Story (stories) (1996)
• A Narrative (2001)
• Eleven Stories (2004)
• Where Three Roads Meet (three linked novellas) (2005)
• The Development (2008)

Nonfiction

• The Friday Book (1984)
• Further Fridays (1995)