While attending high school in Berkeley, California, Schrag self-published her first comic series, Awkward, depicting events from her freshman year, originally selling copies to friends and family. Slave Labor Graphics subsequently reprinted Awkward as a graphic novel, followed by three more books based on her next three years of school: Definition, Potential, and Likewise. The books were republished by Touchstone/Simon & Schuster in 2008 and 2009. The books tell stories of family life, going to concerts, experimenting with drugs, high school crushes, and coming out as a bisexual and later as a lesbian. Killer Films is producing a movie adaptation of Potential; Schrag has written the screenplay.

Schrag graduated from Berkeley High School in 1998. She graduated from Columbia University with a bachelor's degree in English in 2003, and has continued to work as a cartoonist. She lives in Los Angeles, California.

The documentary "Confession: A Film About Ariel Schrag" was released in 2004. It explores then-23-year-old Schrag's world in which she "negotiates fame, obsesses about disease, and discusses the way she sees as a dyke comic book artist."

Schrag is currently a writer for the HBO series How To Make It in America.

Schrag was a writer for the third and fourth seasons of the Showtime series The L Word'".

Schrag is featured on an impressive list of out media professionals in The Advocate's Forty under 40 issue of June/July 2009.