Poor Sena, all of his life from pre-school and on he has been a gopher, running back and forth answering to some bully's every whim. But that's about to change! It's Sena's first year in High School, and Sena has vowed not to get picked on. Then Sena is forced to join the football team because of his speed, but the team Captain, Hiruma, doesn't want anyone in the school to know about him, or he will be forced onto every sports team in the school. So they disguise Sena as EyeShield 21 and put a tinted eye shield on his helmet. And that's where the adventure begins...
Shin stops the passing game of Deimon forcing them to use Sena. Sena tries to pass Shin with the Devilbat Ghost, but Shin simply turns around to stop him with the Trident Tackle. However Shin says there battle is not over, as Sena’s speed was not maxed out. Sena does another run and uses the Devil Light Hurricane (using opponents strength to push himself past), named by Hiruma, to pass by Shin on their third one-on-one. But Shin catches up right away and stops Sena, now also being equal in speed.
Hiruma and the rest of the team go to spy on Ojo at their high school festival to find out about the ballista, but all of the other teammates except Hiruma, Kurita, and Musashi get caught up in the festival, namely a quiz show.
A kid in a wheelchair who idolizes Sakuraba realizes he's not the ace of Ojo. He sulks at a river until Sena and the others cheer him up. He returns and talks to Sakuraba, who says he won't be the ace until he is better than Shin and that's why he trains so much. The kid offers him a wristband that he asks Sakuraba to wear in the game against Deimon.
Panther and a couple of the Devil Bats play a street game against a rival neighborhood to help Panther regain his love of football.
A recap of the Shinryuuji and Hiruma, Kurita,and Musahi's involvement.
The Devil Bats are given a night cruise on a ship to relax before the game. When dinner time comes, it turns out someone has eaten their dinner. Sena is put in charge of finding out who did it. Then a blackout occurs; when power is restored, Mamori's briefcase is missing and Monta has been kidnapped. Sena sees someone running and chases after that person. It turns out that was Shin and the Ojo White knights are also on the boat. The food was eaten by Otawara, Shin caused the blackout, the briefcase was never missing, and Monta was mistaken for a circus monkey and placed in a cage.
Finally, the match with Shinryuji draws near. Doburoku tells Yukimistu that he will participate in this game, much to the team's delight. At Shinryuji, their coach shows them information that they have on the Devil Bats on a waterfall and projection screen, when Agon arrives (with two girls in tow) and says he'll crush them all, Hiruma especially. Sena's face appears on the screen, and Agon suddenly throws one of the underclassmen into the waterfall, adding "And that piece of trash too." At that moment, Sena shudders because he suddenly has a bad feeling. Later that night, Suzuna texts Sena, asking him if he is afraid. Sena (thoroughly peeved) texts back that he's not scared, he just can't believe that this is all happening. Suzuna asks him if this is his goal, to which Sena replies "No, I want to go to the Christmas Bowl, so we'll win, I promise!" With that said, Suzuna smiles in her sleep, saying that she'll be behind him, every step of the way.
After winning the game, the players line up to shake hands. Agon refuses to believe he lost and is about to attack Hiruma but Unsei punches Agon and takes the blame for their team's loss. Agon calms down and says they will beat Deimon next spring. Deimon celebrate their victory with a party while Hiruma sleeps with the video of their previous game on.
Three days before the game between Deimon and Ojo, Hiruma takes the team on a helicopter to make them remember the lines where the defense of Ojo Knights are weakest. The coach makes the team wear masks that greatly reduce their oxygen intake, which will greatly increase their lung intake for one day. The coaches of Deimon and Ojo meet on the field where the game will take place and pour wine onto the grass so the heavens may help the losers of the match "recover" quicker.
Oujo White Knights vs. Sado Strong Golems! The rock-hard bodies of the Golems seem to present Oujo with a problem, but Shin reveals the "completed" version of Spear Tackle, the Trident Tackle. Oujo wins 42:0. In the end Hiruma's father calls him and says he waited for Hiruma at their meeting place but he did not come. His father says he is sorry he cannot see Hiruma at the Christmas Bowl as he has to leave Japan. Before he finishes talking, Hiruma hangs up and throws his cellphone away with his face hidden from the camera.
Hiruma tells Sena that he has to blitz Agon on every play, but it just doesn't seem to work. Once, while Agon is about to pass the ball, he says that they are getting a "game over," which makes Sena suddenly furious, to the point where he forgets he is in a game and jumps to attack Agon, who dodges, but is slightly disturbed. After a while, Shinryuji goes with a run, which in reality is a trap. Sanzo back passes to Agon just as Sena rushes up. Because of Sena's intense concentration on Agon, Sena somehow sees the football, even though it is in his blind spot, and knocks it away with a superhuman jump to the side. Everybody goes for the ball, and Juumonji manages to get it, thanks to Kurita. As he runs with the ball, Agon catches up and stops him. Juumonji, realizing what Sena had to go through, takes one more step and crosses the goal line. It seems that everything will be all right, but then Sena's legs start to have problems, and Doburoku cools them down with an ice pack. In the meantime, Unsui notices that Agon has acknowledged Sena as a rival, and thinks that it's great. An intense rivalry aura develops between Agon and Sena, and Shin once again notes that Sena will be improving to no limits.
At the beginning of the episode Shin comments that even though each individual in Deimon is lacking, as a team they are already regarded as the strongest in Kanto, hinting the result of the game. This episode centers around Monta's individual battle with Ikkyu. Monta wins Ikyuu in an aerial battle by snatching the ball away from him in mid-air, and scores a touchdown by successfully catching a long pass. Ikkyu finally admits Monta as a rival but still states that the 'Number One' in Kanto is still himself. Monta's successful touchdown brought back a momentum to the Devil Bats. Near the end of the episode Agon shows his true strength by imitating Sena's Devil Bat Ghost and passing Sena with it, proving the reign of natural physical talent such as himself as compared to the Sena who had completed the move by intensive training. Sena's knee starts hurting after he used Devil Bat Ghost too many times and caused an 'act' incident between Hiruma and Musashi about the future of a sports player. In the next play, Eyeshield 21 intercepts Unsui's 'Tranquil Reflections' by abandoning the post of defending the prodigy, Agon.
Seibu Wild Gunmen vs. Misaki Wolves! Before the game, the Wolves' long-legged Kamiya Taiga taunts Riku by challenging Sena as his rival. It turns out he's not all talk, and as a result, Riku loses his cool. Could this mean elimination for Seibu?
Riku loses his cool and gets angry at the Wolves. This puts the whole team into frustration. Reassured by his teammates (including a very sick Tetsuma with a cold), Riku regains his calm and returns to the field with the debut of his perfected technique: Rodeo Drive Stampede! The game ends with 21:48, victory for the Gunmen.
Sena grabs the ball and is about to score a touchdown when Agon gets in the way. Agon is about to strike down Sena, but when Agon suddenly insults the Devil Bats' dreams of going to the Christmas Bowl, Sena's newfound fury gets the best of him, and he tries to attack Agon. Agon chops Sena's arm away, and then tries to stop Sena, who uses the Devil Bat Ghost to get away. Agon chases after Sena, who suddenly realizes that the God Speed Impulse won't work on something Agon can't see, so he pushes down on Agon's helmet in his blind spot. Sena actually slams Agon's head into the ground and scores a touchdown, making the score 35:28.
58 seconds remain with the score at 35:28, Shinryuuji leading the Deimon Bats. Deimon must score a touchdown in those 58 seconds to win. After gaining a short amount of yards and spiking to stop the clock, Hiruma pulls a long pass to Monta. Monta catches it and with 4 seconds to go, is tacked by Agon 20 yards from the goal. The timer becomes zero and Deimon loses.
It turns out that before Monta was tackled down, he reached his hand out and grabbed the grass on the "out of bounds area," stopping the clock and regaining those 4 seconds. Within those 4 seconds, Hiruma distracts the other team by causing an uproar in the audience. When it looks like Hiruma is getting the crowd worked up this sets him in motion and the ball is directly snapped to Sena. He runs it but gets covered by Agon. Sena then tosses the ball in the air and Hiruma catches it and scores by running it past Agon. The score is now 35 to 34. Touchdowns are worth 2 points now and kicks are worth one. With no chance to win in a tiebreaker, they must score a touchdown on the last play. Hiruma takes the ball and runs towards the Shinryuuji defense line. He throws the ball in the air and Sena catches it and scores a touchdown, which wins the game 35 to 36.
The first half ends with 32:0, Shinryuji in the lead. The second half begins after Hiruma tells the team to give up and try and not get injured. The team understands he means they should get rough, meaning that Musashi will kick the ball to the outfield. They catch the ball and Yukimatsu joins in for the next play. Yukimitsu knows where Hiruma will throw the ball; this move is called Option route, where Hiruma chooses the best place to throw the ball. Yukimitsu catches it and gets Deimon their first touchdown.
Sena may be on the Deimon Devilbats football team, but he realizes that he doesn't know anything about the game of Football. Can Sena learn how to play, or will he give up before the Spring season?
It is Sena's first day of High School. And from now on his school life will be different. Sena has vowed not to be made a gopher like he has been in the past. But its bad luck for Sena after the Football Team Captain, Hiruma catches Sena running away from the Hah Brothers. Will Sena join the team and help the football team make it to the Christmas Bowl?
Sena and Suzuna go to retrieve their helmets and cleats at a store where Sena sees a helmet with an eyeshield on it. Akaba is revealed to be the owner of the helmet. Akaba proclaims he will defeat Eyeshield 21 and take the title that be believes rightfully belongs to him.
After watching Deimon score so easily with Eyeshield-21's speed, Ojo's coach sends in Shin to put an end to Eyeshield 21.
Sena decides that he needs to get away from having Mamori babying him all the time, so he decides to train alongside the football team, much to her objections.
A "halftime show" of short player-centric stories, interspersed with chibi shorts.
Sena takes up wrestling in order to try to defeat Ivan's mammoth tackle.