He is primarily known as the creator of Sharknife, published by Oni Press. Other works of his include PENG (a Sharknife spinoff about kickball) for Oni, and several video-game-themed comics for UDON including Darkstalkers, Street Fighter, and Rival Schools.
Lewis' work is notable for its combination of global youth culture influences, including martial arts, video games, American comic books and cartoons, Japanese anime and manga, graffitti, hip-hop, and indie rock. His work has often been compared to that of Bryan Lee O'Malley, and the two artists are friends. Lewis' art tends to be extremely stylized and make heavy use of sound effects. So far he has worked almost exclusively in the action genre. Lewis cites Paul Pope and Masashi Kishimoto (creator of Naruto) as his primary comics influences.