Gloeckner was born in 1960 in Philadelphia, and spent most of her later childhood and young adult life in San Francisco, where her family moved in the early 1970s. She attended several Bay Area schools, including The Hamlin School for Girls, Castilleja (in Palo Alto), Urban High School, Lick-Wilmerding High School, The Independent Learning School, and San Francisco State University, where she studied art and biology. She was interested in cartooning from an early age; her father was a commercial illustrator, and through her mother she met several of the San Francisco underground comics figures who were to have a profound influence upon her, including Robert Crumb, Bob Armstrong, Aline Kominsky, Bill Griffith, and Diane Noomin. However, rather than pursue a career in cartooning, she choose to study medical illustration at the University of Texas Southwestern Medical Center at Dallas.

Gloeckner has lived in San Francisco, Dallas, Aix-en-Provence, Paris, Prague, Setauket NY, and Ann Arbor, where she now teaches at the University of Michigan at Ann Arbor, in the School of Art and Design. She has been married three times and has two children.

She was the recipient of a 2008 Guggenheim fellowship.

Her novel and many of her short stories are semi-autobiographical, a frequent cause of comment due to their depiction of sex, drug use, and childhood traumas; however, Gloeckner has stated that she regards them as fiction. Sexual content led to A Child's Life being banned from the public library in Stockton, California after it was checked out by an 11-year-old reader; the mayor of Stockton called the book "a how-to manual for pedophiles".

Less controversial, and actually intended for children, is the book "Weird Things You Can Grow," published by Random House, and books in the series beginning with Tales too Funny to be True published by HarperCollins, for which she did the illustrations.

Solo works

• A Child's Life and Other Stories. (1998; revised edition, 2002) North Atlantic Books. ISBN 1-58394-028-6
• An Account in Words and Pictures. (2002) Frog Press. ISBN 1-58394-063-4

As illustrator

• Ballard, J.G. The Atrocity Exhibition. (1990) RE/Search Publications. ISBN 0-940642-18-2
• Spinrad, Paul. "The RE/Search Guide to Bodily Fluids". (1994). RE/Search Publications. ISBN 0-940642-28-X ( cover image)
• V. Vale (Ed.) and Andrea Juno (Ed). "Angry Women". (1991). RE/Search Publications. ISBN 0-940642-24-7 ( cover image)
• Winks, Cathy, and Anne Semans. The Good Vibrations Guide to Sex, 3rd edition. (2002) Cleis Press. ISBN 1-57344-158-9