Ryan was raised in Ann Arbor, Michigan, where she graduated from Pioneer High School in 1989. Her first novel, Empress of the World, was published in 2001 and is an ALA Best Book for Young Adults. A sequel, The Rules for Hearts, was published in 2007 and won the 2008 Oregon Book Award for Young Adult Literature. She also writes graphic novels and is a member of the Periscope Studio.
Openly bisexual, she is married to the cartoonist Steve Lieber.