Born in Stockholm, Spiegelman started out as a comic strip artist in a series of underground magazines, including Real Pulp, Young Lust and Bizarre Sex. He also illustrated many of the Wacky Packages stickers. He founded Arcade along with Bill Griffith) and RAW with his wife Françoise Mouly in 1980.
In 1986, he released the first volume of Maus (Maus: A Survivor's Tale) which retraced his parents' story of survival of the Holocaust. The second volume, Maus: from Mauschwitz to the Catskills (also known as Maus: My Father Bleeds History) followed in 1991.
Spiegelman worked for the New Yorker Magazine but resigned a few months after the September 11 terrorist attacks. Spiegelman's post-September 11 New Yorker cover received wide acclaim. The cover at first appears to be a totally black, but upon close examination reveals the silouettes of the World Trade Center towers in a slightly darker shade of black.
Spiegelman states that his resignation from the New Yorker was to protest the "widespread conformism" in the United States media. Spiegelman is a sharp critic of the administration of President George W. Bush and claims that the American media has become "conservative and timid". Spiegelman claims that the New Yorker censored his work including a 4th of July cover containing an atomic bomb and a Thanksgiving issue showing U.S. military aircraft dropping turkeys over Afghanistan and titled "Operation Enduring Turkey".
He is currently working on In the Shadow of No Towers, a strip where he relates his experience of the Twin Towers attack and the psychological after-effects.
Spiegelman is a prominant advocate for the medium of comics. He tours the country giving a lecture he calls "Commix 101." He and Mouly also edit a series of hardcover comic anthologies (of mostly newly commissioned work) for children, called "Little Lit."