Despite being a talented artist, middle school student Moritaka Mashiro is unsure about his future, accepting that he will simply lead a normal life. After seeing one of Mashiro's drawings in class, Akito Takagi—an aspiring writer—insists that they write a manga together. But Mashiro is hesitant—his uncle, a mangaka, had died from overworking just a few years prior. However, when Mashiro hears that his crush, Miho Azuki, aims to be a voice actress, he becomes determined to create a manga that can be adapted into an anime for her to star in. Reciprocating Mashiro's feelings, she agrees to get married once they have both achieved their dreams.

Bakuman. chronicles Mashiro and Takagi's successes and struggles in their attempts to be serialized in Weekly Shounen Jump and become famous mangakas. Will their gamble pay off, or will they join the countless number of failures?