Begin as a webcomic before being published.
Set in a fictional version of Tokyo, Megatokyo portrays the adventures of Piro, a young fan of anime and manga, and his friend Largo, an American video game enthusiast. The manga often parodies and comments on the archetypes and clichés of anime, manga, dating sims and video games, occasionally making direct references to real-world works. Megatokyo originally emphasized humor, with continuity of the story a subsidiary concern. Over time, it focused more on developing a complex plot and the personalities of its characters.

Megatokyo was nominated in at least one category of the Web Cartoonist's Choice Awards every year from 2001 through 2007. It won Best Comic in 2002, as well as Best Writing, Best Serial Comic, and Best Dramatic Comic. The largest number of nominations it has received in one year is 14 in 2003, when it won Outstanding Environment Design. The series tied with Svetlana Chmakova's Dramacon for the 2007 Best Continuing OEL Manga.