Shary Flenniken grew up in Alaska, Panama and Seattle, where she studied at a commercial art school. She began working on small-press comics in Seattle and moved in 1971 to San Francisco, where she joined the Air Pirates collective. She was a marginal contributor to the Air Pirates, and the only member not to be sued for their Disney parodies.

She was later widely recognized as an influential figure in the integration of feminist concerns into underground comics. Air Pirates co-founder Bobby London was married to Flenniken for several years.

Flenniken and London were recruited by National Lampoon for regular comics features; Trots and Bonnie appeared there from 1972 to 1990. Flenniken was an editor of National Lampoon from 1979 to 1981, recruited many of the magazine's best-known cartoonists during that time, and co-wrote the screenplay of National Lampoon Goes to the Movies.

Her second marriage was with the late Bruce Jay Paskow of the band Washington Squares. After the couple wed in 1987, they moved two years later from Manhattan to Seattle, where they were together for six years until Paskow's death in 1995.

Flenniken edited Seattle Laughs: Comic Stories about Seattle (Homestead, 1994), and she continues to freelance from Seattle. In addition to contributions to DC Comics' Paradox Press anthologies, her work has appeared in Mad, Premiere, Details, The American Lawyer and other magazines. In recent years she contributed to the Graphic Classics series, praised by School Library Journal and Publishers Weekly for its adaptations of Mark Twain, O. Henry and other authors.