Collaborating with Dave Cooper under the pen name "Hector Mumbly", Ryan's comics appeared in nearly every issue of Nickelodeon Magazine. Cooper and Ryan also collaborated on a "Wonder Woman vs. Supergirl" story for the DC Comics anthology Bizarro. Ryan collaborated with Peter Bagge in both Angry Youth Comix and Bagge's Hate Annual, in addition to penciling and inking two stories for Bagge's DC series Sweatshop. In 2006, Ryan guest-edited a special comics issue of Vice magazine, which included contributions from over thirty of Ryan's comics contemporaries.
Ryan's illustrations have appeared in MAD, LA Weekly, National Geographic Kids, Hustler Magazine, The Stranger, and elsewhere. Ryan has also done work for clients such as Nobleworks greetings cards, Rhino Records, and Fox TV. His comics have been translated into Spanish, Portuguese, and French. Angry Youth Comix was nominated for a Best Mini Ignatz Award at the 2000 Small Press Expo. It has since been nominated for multiple Harvey and Eisner Awards. "Prison Pit" won an award for "Best Lettering" at the Stumptown small press festival in Portland, OR in April 2011.