Isagi Yoichi, a first-year forward, loses his chance for the Nationals because he has passed the ball to his fellow player in front of the goal. That's when he receives an invitation for Blue Lock. It's a facility to train one world's greatest striker out of 300 high-school-aged forwards so that Japan can win the World Cup.

Kira is eliminated from Blue Lock, and with that, the first day at the Blue Lock that promises to create the greatest center forward in the world begins in Isagi Yoichi 's life.

The first selection is the round-robin tournament of five teams of V, W, X, Y and Z in Building Five, with only top two teams being eligible to move forward. Isagi's Team Z, the lowest ranking team, plays against Team X. But because of the special rule that allows the top scorer of the team to proceed to the next section, the match turns into chaotic scrambling for the ball, regardless of the teams. It was Barou Shoei, Team X's formidable striker, who changes the flow of the game.

Team Z was crushed by Team X, who centered the offensive play around egoistical yet skilled Barou. Responding to Ego's urge to "take up a weapon," the players discuss what their weapons are in preparation for the next match. However, Isagi struggles to identify what it is. Using "the smell of the goal" he felt in the game against Team X as a hint, Isagi and the others go against Team Y in the next match.

Isagi relies on "the smell of the goal," his raw instincts, to make a move, and it leads to the fierce battle of "reading" each other's hand with Team Y's playmaker, Niko Ikki. Isagi and Niko's battle as they both watch over the whole field and throw their ego at each other, brings them to the last one minute of the match. Can Isagi and Team Z beat Niko's final strategy, "One Time Kill Counter"?

After the match with Team Y, Isagi's rank moved up, and he became the center of the team. The next match is against Team W, led by the Wanima twins. Their eye contact and impeccable combinations are hard to beat. They used to play in the same team as Chigiri Hyoma, and they use his past trauma to egg him on. Chigiri says that he joined Blue Lock to find a reason to quit soccer. Team Z leads the game with Kuon's play. Everyone's elated for the good start of the match, but Isagi feels something is off.

Because of Kuon’s betrayal, Team Z is faced with a desperate situation of playing 12-on-10, with the opponent knowing everything about their weapons and strategies. Even under such a circumstance, Team Z never gives up on the fight, and Isagi continues to believe in himself. Inspired by their passion, Chigiri runs through the field at an incredible speed, his weapon he has sealed away. His ego rocks the match when they are losing at 3-4.

The Z team has only one game left to play, and it will decide the future of its members. While everyone seems to be nervous about the kickoff, Isagi is trying to find a way to score goals without anyone's help.

The match continues to leave Team Z scared of Nagi's abilities. However, one of the members is not scared, even though they are facing a soccer genius...?

Each player unleashed their weapon and ego, and Team Z has caught up to a draw. They totally have the momentum of the game, but that has “awakened” Team V’s monster, Nagi. In the chain reaction to awakening, Isagi also learns to use his weapon and keeps fighting. The “heat” generated by the clashing of ego from both teams starts to affect Kuon as well.

Team Z launches a final counter to try and win against Team V. Isagi is trying to find the last piece he needs to crack the formula to become a goal machine.

Isagi and his friends barely manage to win as Barou awakens as the "villain" of the field. In order to cause a further "chemical reaction", they take away the only player who showed their ego to "eat" themselves and advance to the force stage. On the other hand, Bachira, who is looking for an opponent for the next match with TOP3, sees through the existence of a "Monster" in himself during training with Rin, and faces his own "ego".

Rin chooses to add Isagi to his team, and together with Bachira they pass the second selection. Waiting for them on the other side is a 5-on-5 match against a team of world-class players. Thanks to Isagi, Bachira, and Rin's coordinated play, they manage to score the first goal, but they soon find themselves overwhelmed by the opposing team's superior skill and ability. Despite this, they desperately keep fighting until the last second, unleashing their own "egos." As a result, the "Blue Lock" project, aiming to produce the world's greatest striker, enters a new phase.