Following a disappointing elimination from the 2018 World Cup, the Japan Football Union, desperate to revolutionize the sport, hires the eccentric and ruthless coach Jinpachi Ego. His controversial solution to the national team's failures is the Blue Lock project, a high-stakes training program designed to forge the world's greatest egotistical striker. To achieve this, 300 of the nation's most talented high school forwards are gathered and imprisoned within a specialized facility. They are forced into a brutal survival-of-the-fittest competition where only one will emerge as the ultimate ace. Those who fail are banned from ever representing Japan on the national team.

The story centers on Yoichi Isagi, a modest and analytical second-year high school forward from Ichinan High. Tormented by a critical moment in his past where he passed up a potential game-winning goal for the sake of teamwork, Isagi enters Blue Lock with a burning desire to discover his own ego and become the best in the world. Initially ranked near the bottom at 299th, he is placed in Team Z, a group of fellow underdogs. Through intense psychological and physical trials, Isagi begins to hone his exceptional spatial awareness and direct shot, slowly evolving from a passive playmaker into a predator who devours his opponents' strengths for his own goals.

The series features a deep ensemble of driven and eccentric players. Meguru Bachira is an energetic and intuitive dribbler who seeks a fellow "monster" to play with. Rensuke Kunigami is a powerful and idealistic left-footer committed to fair play. Hyoma Chigiri is a talented speedster haunted by a past leg injury that limits his potential. Seishiro Nagi is a lazy prodigy with world-class trapping skills who only discovered soccer out of boredom. Other key rivals include Shoei Barou, a domineering and self-proclaimed "king" of the field, and Rin Itoshi, a cool and technically perfect prodigy playing in the shadow of his genius older brother, Sae Itoshi. Overseeing the entire program is Jinpachi Ego, whose harsh philosophy emphasizes individual ego over collective harmony, and his assistant, Anri Teieri, a passionate staff member who believes in the project's potential.

The narrative is structured in distinct, escalating arcs. The Introduction Arc establishes the creation of Blue Lock and the initial culling of players. The First Selection Arc divides the 300 survivors into 25 teams of five within five different stratums. Team Z must survive a round-robin tournament, culminating in a decisive match against the undefeated Team V, led by Nagi and his partner Reo Mikage. The Second Selection Arc raises the stakes dramatically, forcing players into individual five-on-goal drills and a series of 3v3 and 4v4 matches where the winning team can steal a player from the losers, forcing former teammates to betray one another. This arc introduces Rin Itoshi as the facility's top player and pairs Isagi with Bachira, Nagi, and Barou to challenge him. The Third Selection Arc sees the remaining 35 players divided into three teams, competing for a spot on the "Blue Lock Eleven," a select squad formed to face the Japan U-20 national team. The first season concludes as this final lineup is chosen.

The second season, subtitled vs. U-20 Japan, covers the U-20 Arc. Here, the fate of the entire Blue Lock project hangs on a single, high-stakes match. The newly formed Blue Lock Eleven must defeat the official Japan U-20 team to secure their right to represent the nation. They face overwhelming odds, including the genius playmaker Sae Itoshi and the explosive and uncontrollable striker Ryusei Shidou, who briefly joins the U-20 side. This arc forces Isagi and his rivals to push past their limits, resulting in a climactic and unpredictable finale. Following this victory, a third season has been announced, which will adapt the Neo Egoist League Arc, where Blue Lock players are integrated into U-20 teams from top footballing nations like Germany, England, and Spain for the final selection to form the U-20 World Cup team.