Hyper Sports, which use extreme gear as support items, have become popular hobby competitions among both children and adults. Hiyori Hayama is a high school singer who has nothing to do with Hyper Sports, but a certain incident sets the story in motion.

Kobayakawa Sena is a little guy who always get picked on by the bullies in school. Since elementary school, he always play the role of the errand boy to the extent that he has become swift and fast in his movements. Coincidentally, Hiruma Youichi and Kurita Ryukan are looking for a fast running back for their American Football team (Amefuto) and want to put Sena in the team. To hide their new star player from the eyes of other High Schools, Hiruma encases Sena in a Amefuto helmet with a dark visor and name him Eyeshield #21.