The whole series was streamed in English by Crunchyroll, while Sentai Filmworks licensed the series, with distribution from Section23 Films on DVDs. The anime series was later licensed in North America by Toonami Jetstream as a joint effort with Viz Media and aired in December 2007, on its site, but before its completion, the streaming service was shut down. In North America, the manga was released by Viz Media from April 2005 to October 2011. The Eyeshield 21 franchise has spawned two original video animations (OVAs), audio albums, video games, and other merchandise. The television series first aired on Japan's TV Tokyo network from April 2005 to March 2008.

An anime adaptation consisting of 145 television episodes was co-produced by TV Tokyo, NAS, and Gallop. The series consists of 333 chapters collected in 37 tankōbon volumes. The manga was originally serialized in Shueisha's Weekly Shōnen Jump from July 2002 to June 2009.

Inagaki chose American football as a central subject of Eyeshield 21 after realizing that it fit perfectly with his idea for the series. The series tells the story of Sena Kobayakawa, an introverted boy who joins an American football club as a secretary, but after being coerced by quarterback Yoichi Hiruma, becomes the team's running back, whilst wearing an eyeshield and the number 21, under the pseudonym of 'Eyeshield 21'. Eyeshield 21 ( Japanese: アイシールド21, Hepburn: Aishīrudo Nijūichi) is a Japanese manga series written by Riichiro Inagaki and illustrated by Yusuke Murata.

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