Barry is best known for her weekly comic strip "Ernie Pook's Comeek". She garnered attention with her 1988 illustrated novel "The Good Times are Killing Me", about an interracial friendship between two young girls, which was adapted into a play. Her second illustrated novel, "Cruddy", first appeared in 1999. Three years later she published "One! Hundred! Demons!", a graphic novel she terms "autobifictionalography". "What It Is" (2008) is a graphic novel that is part memoir, part collage and part workbook, in which Barry instructs her readers in methods to open up their own creativity; it won the comics industry's 2009 Eisner Award for Best Reality-Based Work.