Her father was a meat-cutter of Irish and Norwegian descent, and her mother, a hospital housekeeper, was of Irish and Filipino descent. Barry grew up in Seattle, Washington in a racially mixed working-class neighborhood, and recalls her childhood as difficult and awkward. Her parents divorced when she was 12. By age 16, she was working nights as a janitor at a Seattle hospital while still attending high school, where her classmates included artist Charles Burns. Neither of Barry's parents attended her graduation. Her mother strongly disapproved of Lynda's love of books and desire to go to college; she said they were a waste of time, and that it was time for Lynda to get a job.

At The Evergreen State College in Olympia, Washington, Barry met fellow cartoonist Matt Groening. Her career began in 1977 when Groening and University of Washington Daily student editor John Keister each published her work without her knowledge in their respective student newspapers, titling it Ernie Pook's Comeek.

Barry was known as the class cartoonist in her grade school. While studying fine arts at The Evergreen State College, she began drawing comic strips compulsively when her boyfriend left her for another girl: "I couldn't sleep after that, and I started making comic strips about men and women. The men were cactuses and the women were women, and the cactuses were trying to convince the women to go to bed with them, and the women were constantly thinking it over but finally deciding it wouldn't be a good idea." These were the cartoons Groening and Keister published as Ernie Pook's Comeek. Barry also credits her start in comics to Evergreen State professor Marilyn Frasca, saying, "The lessons I learned from her when I was 19 and 20, I still use every day and have never been able to wear out."

After graduating from Evergreen, Barry moved to Seattle. When she was 23, the Chicago Reader picked up her comic strip, enabling her to make a living from her comics alone. She later moved to Chicago, Illinois. As she described her career start:
[Editor] Bob Roth called me from the Chicago Reader as the result of an article [her college classmate] Matt [Groening] wrote about hip West Coast artists — he threw me in just because he was a buddy, right? And then Bob Roth ... called and wanted to see my comic strips, and I didn't have any originals. I didn't know anything about originals, that you don't give them to newspapers because newspapers lose them. So I had to draw a whole set that night and Federal Express them. So I did, and he started printing them, and he paid $80 a week, and I could live off of that. And because he's with this newspaper association, the other papers started picking it up. So it was luck. Sheer luck. [Matt] got into the Los Angeles Reader. For a long time the Los Angeles Reader wouldn't print me, and the Chicago Reader wouldn't print Matt even though they're sister publications. So we both worked on the publishers and the editors to get each other in. It was really funny: when we got into each others' papers, everything sort of took off for both of us.

Collections of her work include Girls & Boys (1981), Big Ideas (1983), Everything in the World (1986), The Fun House (1987), Down the Street (1989), and The Greatest of Marlys (2000). In 1984, she released a coloring book with brief text called Naked Ladies! Naked Ladies! Naked Ladies! She also wrote and drew a full-page color strip examining the everyday pathology of relationships for Esquire magazine. In 1989 Barry's strip appeared weekly in more than 50 publications, mostly alternative newspapers in large cities.

Barry has described her process as developing a story while working, not planning it out in advance. In answering a question about her book What It Is in an interview with Michael Dean for The Comics Journal, Barry said:

"There were big realizations and small ones. The biggest one was the same one I had when I wrote Cruddy. The realization that the back of the mind can be relied on to create natural story order. It's not something I have to try to do, or think too hard about. If I just work every day on a particular project, it seems to begin to form itself if I keep moving my hands while maintaining a certain state of mind."

Due to the loss of weekly newspaper clients, Barry moved her comics primarily online by 2007.

Collections of Barry's comics began appearing in 1981. She has written two illustrated novels, The Good Times are Killing Me (1988) and Cruddy, also known as Cruddy: An Illustrated Novel (1999).

Cruddy is written in the voice of a fictional girl named Roberta Rohbeson, who describes her home as ""the cruddy top bedroom of a cruddy rental house on a very cruddy mud road" and who ends up in a string of violent adventures with her father. Barry addressed the violence in the book in an interview with Hillary Chute in The Believer, saying:

"Cruddy has murder galore. It's, like, you know, it's murder fiesta, and lots of knives and killing. ... So does that mean that I'm a person who thinks about murder? Well, yes, as a matter of fact, I do think about murder constantly. Actually, when I'm talking to people who are driving me crazy, I often imagine they have an ax in their forehead while they're talking to me. I know that that's my personal relationship with murder and knives and blood. It doesn't mean that I need to go do that."

The book was well regarded by critics. Alanna Nash wrote in The New York Times that "the author's ability to capture the paralyzing bleakness of despair, and her uncanny ear for dialogue, make this first novel a work of terrible beauty." In The Austin Chronicle, Stephen MacMillan Moser wrote a review in the form of a letter to Barry, saying "You blew me away. Sometimes I wasn't sure if something was supposed to be funny or not, but I laughed a lot. But I also feel like I got run over by a bus." In 2013, English professor Ellen E. Berry, published a paper focused on the novel titled "Becoming‐Girl/Becoming‐Fly/Becoming‐Imperceptible: Gothic Posthumanism in Lynda Barry's Cruddy: An Illustrated Novel." Berry wrote in her summary of the paper that the book is "a vivid example of what I call 'gothic posthumanism' in which gothic themes and tropes serve to advance an extensive critique of anthropo‐ and other centrisms, all forms of domination, the values of liberal humanism and affirmative conformist culture." Berry analyzes Cruddy using a theory of posthuman ethics articulated by Rosi Braidotti, writing that she used Braidotti's theory "to analyze Roberta's survival strategies and her radically posthuman identification with animals centering on their shared vulnerability and thus their shared goal: to disappear and to survive."

Barry adapted The Good Times are Killing Me as an Off-Broadway play (see below).

One! Hundred! Demons! first appeared as a serialized comic on Salon.com; according to the book's introduction, it was produced in emulation of an old Zen painting exercise called "one hundred demons." In this exercise, the practitioner awaits the arrival of demons and then paints them as they arise in the mind. The demons Barry wrestles with in this book include regret, abusive relationships, self-consciousness, the prohibition against feeling hate, and her response to the results of the 2000 U.S. presidential election. The book contains an instructional section that encourages readers to take up the brush and follow her example. According to Time magazine, the book uses "acutely-observed humor to explore the pain of growing up."

Barry has also published four books about the creative processes of writing and drawing. Making Comics, What It Is, Picture This, and Syllabus: Notes From an Accidental Professor focus on opening pathways to personal creativity. Publishers Weekly gave Syllabus a starred review, calling it "an excellent guide for those seeking to break out of whatever writing and drawing styles they have been stuck in, allowing them to reopen their brains to the possibility of new creativity." The AV Club named Syllabus one of the best comics of 2014.

Barry adapted her illustrated novel The Good Times are Killing Me (1988) as an off-Broadway play that had 106 performances from March 26 to June 23, 1991, at the McGinn-Cazale Theatre at 2162 Broadway, and 136 performances from July 30 to November 24, 1991, at the Minetta Lane Theatre. It was directed by Mark Brokaw and produced by Second Stage Theatre, with the Minetta Lane portion produced by Concert Productions International. Angela Goethals won a 1990–91 Obie Award for her lead role as Edna Arkins. Chandra Wilson as Bonna Willis won a 1991 Theatre World Award. Barry was nominated for the 1992 Outer Critics Circle's John Gassner Award.

In its March–April 1991 issue, MNother Jones published Barry's essay "War", which protested the first Gulf War: "War becomes part of our DNA...How dare anyone purposefully bring it into our lives when other options remain?" Barry had previously read the essay on Chicago Public Radio's program "The Wild Room," which she co-hosted with Ira Glass and Gary Covino.

Barry offers a workshop titled "Writing the Unthinkable" through the Omega Institute in Rhinebeck, New York, and The Crossings in Austin, Texas, in which she teaches the process she uses to create all of her work. Barry conducts approximately 15 writing workshops around the country each year. She credits her teacher, Marilyn Frasca at The Evergreen State College, with teaching her these creativity and writing techniques. Many of these techniques appear in her book What It Is. A New York Times article about her writing workshops summed up her technique: "Barry isn't particularly interested in the writer's craft. She's more interested in where ideas come from—and her goal is to help people tap into what she considers to be an innate creativity."

For a time, Barry dated public-radio personality Ira Glass. She briefly joined him in Washington, D.C., but a few months later, in the summer of 1989, she moved to Chicago to be near fellow cartoonists.  Reflecting on the relationship, she called it the "worst thing I ever did," and said he told her she "was boring and shallow, and...wasn't enough in the moment for him." She later drew a comic based on their relationship titled "Head Lice and My Worst Boyfriend", which was later included in her book One! Hundred! Demons!...

Barry is married to Kevin Kawula, a prairie restoration expert. They met while she was an artist in residence at the Ragdale Foundation and he was land manager of the Lake Forest Open Lands project in Lake Forest, Illinois. In 2002 they moved to a dairy farm near Footville, Wisconsin.

Barry is an outspoken critic of wind turbines and has lobbied the Wisconsin government for clearer zoning regulations for turbines being built in residential areas. She has also spoken out about wind power's problems with noise pollution, human health, and efficiency as related to variability.

In 1994, Barry suffered a near-fatal case of dengue fever.

References

Kirtley, Susan E. (2012). Lynda Barry: Girlhood through the Looking Glass. University Press of Mississippi. ISBN 978-1-61-703234-9.

Chute, Hillary (November–December 2008). "Somehow People Started Somehow to Actually Start to Like It, ..." The Believer. 6 (9): 47–58.

Tensuan, Theresa M. (Winter 2006). "Comic Visions and Revisions in the work of Lynda Barry and Marjane Satrapi". Modern Fiction Studies. 52 (4): 947–964. doi:10.1353/mfs.2007.0010.

Chute, Hillary L. (2010). Graphic Women: Life Narrative and Contemporary Comics. New York: Columbia University Press; ISBN 978-0-231-15062-0.

Dean, Michael (March 2, 2009). "Lynda Barry Interview". The Comics Journal (296). Online excerpts from print interview. Archived from the original on May 11, 2009.

Lynda Barry profile, Lambiek Comiclopedia

Salon.com: Lynda Barry archive, salon.com; accessed March 5, 2016.

"Lynda Barry intreview". Drawn and Quarterly. Archived from the original on November 22, 2012. Retrieved February 23, 2013.