Founded in 1942 as an independent publishing house in New York City by Kurt and Helen Wolff, it specialized in introducing progressive European works to American readers.

[6] Pantheon Books was founded in 1942 in New York City by Helen and Kurt Wolff who had come to the United States to escape fascism and the Holocaust.

Important early works published by Pantheon were Zen and the Art of Archery by German scholar Eugen Herrigel, the Bollingen series (composed of C. G. Jung's collected works in English and books of noted Jungian scholars), the first complete translation of the I Ching, and Boris Pasternak's Doctor Zhivago.

[7] When Random House bought Alfred A. Knopf in 1960, the front page of the New York Times reported that the merger "united two of the nation's most celebrated publishers of quality writing".

By the late 1960s, Pantheon started to bring American writers such as Noam Chomsky, James Loewen and Studs Terkel to European readers.

[13] In protest at Schiffrin's forced resignation and other changes in staffing, such as the hiring of Erroll McDonald, editors and staff Tom Engelhardt, Wendy Wolf, Sara Bershtel, Jim Peck, Susan Rabiner, David Sternbach, Helena Franklin, Diane Wachtell, Gay Salisbury, and several others resigned in the following months.

[12][13][14] Authors of books published by Pantheon, Random House, and other related imprints, including Studs Terkel, Kurt Vonnegut Jr., Princeton historian Arno Mayer, and Barbara Ehrenreich, held a protest outside Random House in March 1990 during which they argued that the termination of Schiffrin amounted to corporate censorship of the books that would not be printed without him.

Again, Schiffrin protested, noting that in the eight years since Random House had come under the direction of Vitale, "Random House's 'high end'—the literary translations and books of criticism, cultural history and political analysis that had built the reputation of the Knopf and Pantheon imprints—were being sacrificed" and that concerns for the "bottom line" would outweigh intellectual and social concerns.

[25] Notable cartoonists whose graphic novels have been published by Pantheon include Spiegelman, Ware, Dan Clowes, Charles Burns, Ben Katchor, Marjane Satrapi, and David Mazzucchelli.

It has published many critically acclaimed graphic novels and comics collections, including Ice Haven, La Perdida, Read Yourself RAW, Maus, In the Shadow of No Towers, and Black Hole.