Plot
Sena Kobayakawa is a timid and physically unremarkable student at Deimon Private Senior High School in Tokyo. Despite his frail appearance, he possesses exceptional speed and agility. These unique talents are recognized by the school's American football team captain, Yoichi Hiruma, who forcibly recruits him as the Deimon Devil Bats' running back. To protect Sena from rival teams seeking to recruit him, he is concealed under the alias "Eyeshield 21", playing while wearing a helmet with an eyeshield and publicly serving as the team's manager.
The team's initial foray into the spring tournament ends in a decisive defeat against the dominant Ojo White Knights, highlighting their inexperience. The team's true focus becomes the fall tournament, a single-elimination tournament where Tokyo's top teams vie for a chance to advance to the Christmas Bowl, the championship game between the best high school teams from the Kantō and Kansai regions. Determined to build a competitive team, Hiruma, Sena, and head lineman Ryokan Kurita assemble a ragtag group of players. This includes former baseball player Tarō "Monta" Raimon, who becomes the team's star wide receiver, and several delinquents who fill out the offensive line. Their shared ambition is to reach the Christmas Bowl, a particularly urgent goal for the second-year students as a school rule prohibits third-year students from participating in club activities.
The team engages in rigorous training and exhibition matches, including a notable game against the visiting NASA Aliens from the United States. During this match, Sena befriends their running back, Patrick "Panther" Spencer, a former ball boy. The team then travels to the United States for intensive training under their former mentor, Doburoku Sakaki, enduring a grueling trek through the desert that forges stronger bonds and culminates in Sena revealing his true identity to his teammates.
Upon returning to Japan, the revitalized Devil Bats enter the fall tournament. As they advance, Sena learns the "Eyeshield 21" moniker originally belonged to a Japanese-American player from Notre Dame High School. After securing a place in the Kantō tournament, the team overcomes formidable opponents, including the Shinryuji Naga, led by the ruthless prodigy Agon Kongo, and a rematch against the Ojo White Knights. They ultimately win the Kantō championship, earning their place in the Christmas Bowl. There, they face the undefeated Teikoku Alexanders from Osaka, led by Takeru Yamato, the original Eyeshield 21. In a dramatic finish, the Devil Bats win the championship, and Yamato acknowledges Sena as the rightful successor to the Eyeshield 21 legacy.
Subsequently, Sena is invited to study at Notre Dame High School in America. Upon returning to Japan, he enrolls at Enma University, reuniting with former teammates and rivals who now play for various university and company teams. Together, they vow to compete for the Rice Bowl, Japan's national football championship.
In a later bonus chapter, the NFL's International Player Pathway Program offers a single spot with the San Antonio Armadillos to a Japanese player. Sena, now playing for the Enma Fires, and Hiruma, of the Saikyodai Wizards, compete against one another in the Koshien Bowl to determine the candidate. Although the Enma team is implied to be victorious, the final selection is not revealed.