In Eyeshield 21, shy, reserved, and small-statured Sena Kobayakawa spends his days at Deimon High School trying to stay out of trouble, yet his size makes him an easy target for bullies. Years of running errands have left him unusually agile, and his habit of slipping through crowds has given him the kind of quick feet that catch the eye of Youichi Hiruma, the cunning captain of the Deimon Devil Bats football team.
Hiruma coerces Sena into joining the squad, then keeps rival clubs from learning his identity by making him play beneath the visored helmet of "Eyeshield 21," a mysterious running back who wears the number 21 jersey. The legend surrounding Eyeshield 21 says he can run at the speed of light and once achieved remarkable feats in the United States during his time at Notre Dame College.
What begins as a way to hide Sena's talent becomes the foundation for his growth as a player and as a person. As he takes part in the Deimon Devil Bats' push through American football, Sena slowly gains confidence, learns to trust his teammates, and forges the bonds that turn him into the team's secret weapon.