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Ryuko Matoi transfers into Honnouji Academy, a high school dominated by its fearsome student council, who wear powerful Goku Uniforms that grant them superhuman abilities. Searching for clues to her father's murder, Ryuko confronts the student council president, Satsuki Kiryuin, saying she is looking for the owner of the other half of a giant scissor blade she wields.

Weakened by her battle, Ryuko flees Honnouji Academy before collapsing in the street. Rescued, she's given food and shelter for night, and upon returning to the Academy faces off against Omiko Hakodate, the Girls' Tennis Club Captain, to repay the favor.

Having kept her end of the bargain, Ryuko demands answers from her homeroom teacher, Aikuro Mikisugi, and learns the secret behind the power of Senketsu and the Goku Uniforms. Meanwhile, Satsuki Kiryuin returns home to claim a power of her own.

While Senketsu is laundered, Ryuko is faced with "No-Late Day", a school event where students must navigate a trap-filled obstacle course and reach school on time, or else they will be expelled. She and Mako make their way across the perilous course, along with an injured girl named Maiko Ogure, while Mako's family attempt to deliver Senketsu to Ryuko. After hijacking an armored bus, the girls manage to make it to the school grounds with 15 minutes left. However, Maiko is revealed to be a member of the disciplinary committee, who steals Senketsu and puts it on herself in a bid to overthrow Satsuki. However, she is immobilized by the freshly washed Senketsu's starchiness, allowing Ryuko to retrieve him. With five minutes remaining, Maiko sets off one more trap to send Ryuko and Mako back to the start of the course. They two fortunately reach class on time using an express cable car, while Maiko is expelled for her treachery.

A mysterious sniper named Tsumugu Kinagase attempts to assassinate Ryuko, but is interrupted by the gardening club, who he manages to defeat. After dealing with the biology club, Ryuko is attacked by Tsumugu, who pins her down and attempts to force her to strip, but is forced to retreat when he is interrupted by Aikuro. As Aikuro and Tsumugu talk later that night, Tsumugu explains that the Kamui could prove a great threat if left alone. The next day, Ryuko confronts Tsumugu, who attacks her with needles that drain power from Goku Uniforms and Kamui, whilst they both come under attack by the gardening, rakugo and hyakunin-isshu clubs. With the clubs wiped out and Ryuko backed into a corner, Senketsu gives himself up to protect Ryuko, but Mako stands up to Tsumugu and returns Senketsu to Ryuko. As Tsumugu comes to understand the bond between Ryuko and Senketsu, they are confronted by one of the four elites, Nonon Jakuzure, but manage to escape.

After learning of his connection with Tsumugu, Ryuko tries to press Aikuro for more information, but does not get much outside of his organization's name, Nudist Beach. Meanwhile, another of the Elite Four, Uzu Sanageyama, gets permission from Satsuki to fight against Ryuko himself. The next day, Uzu challenges Ryuko, facing against her in his Three-Star Goku Uniform, Blade Regalia. He has the advantage due to his fast eyesight reading all of Ryuko's moves, but Ryuko overcomes this by using a part of her uniform to block Uzu's vision, allowing her to defeat him and destroy his uniform. Not wanting to give up, Uzu undergoes a drastic operation to sew his eyes shut, and challenges Ryuko again, this time using his other senses to predict her moves and completely overwhelm her. However, before Uzu can deliver the final blow, his Goku Uniform overheats due to him being more powerful than it can handle, giving Ryuko the opportunity to escape.

Hearing about how many students have been starting their own clubs in order to become eligible to get better uniforms, and thus better living rights, Ryuko decides to start her own Fight Club, assigning Mako as the club president to handle all the paperwork and meetings. As Ryuko increases the club's reputation by defeating other club presidents, Mako manages to earn a One-Star Goku Uniform, upgrading the Mankanshoku family to a better apartment. Mako's determination to preserve her family's newfound happiness moves the family up to an even more luxurious lifestyle. However, as Mako becomes more serious about her duties as club president and the other family members indulge in their wealth, Ryuko starts to feel lonely as the family finds less time to spend together. Just as Ryuko decides to resign from the Fight Club, Satsuki gives Mako a Two-Star Goku Uniform, telling her to defeat Ryuko if she wants to keep her life of luxury. Ryuko decides to take the brunt of Mako's attacks, which leads to Mako eventually realizing the error of her ways, deciding to disband the Fight Club and return to her life in the slums. Meanwhile, Satuski reveals that by using Ryuko to purge the weaker clubs, she will restructure the student council by holding a reprisal general election.

Satsuki announces her new election system in which students must survive a seven-day battle against each other in order to stand out on top and earn Goku Uniforms, sending the entire school into a state of emergency. Meanwhile, Ryuko takes Mako to the ruins of her old house, where she tells her about the circumstances surrounding her father's death. Finding no further clues in the basement where she found Senketsu, Ryuko and Mako head home, only for their scooter to run out of gas. They end up encountering the disciplinary committee chair and one of the Elite Four, Ira Gamagoori, who, having just attained his driving license and is taking the week off, offers to take them to a gas station. During their drive, they are attacked by the automotive and airsoft clubs, who are targeting Ira's Three-Star Goku Uniform, Shackle Regalia. Recalling how he first met Satsuki, Ira unleashes his uniform, which uses the power of masochism to evolve into Scourge Regalia and lay waste to his opponents. After a week passes, Honnouji's strongest assemble for the Sudden Death Runoff Election, with only Ryuko and the Elite Four making their way to the top. There, Satsuki challenges Ryuko to defeat each of the Elite Four in exchange for details concerning her father's death, her first opponent being Ira.

As Ryuko awaits the time for her battle against Ira, Aikuro asks her to drop out of the match, warning that she is not ready to face the Elite Four, to which she naturally declines. The battle soon begins, with Ira activating his Shackle Regalia, attacking himself in order to provide the power needed to transform into Scourge Regalia. Ryuko soon learns that the Shackle Regalia also serves as an armor protecting its life fibers. This pushes Ryuko into a corner, as she is unable to damage the Shackle Regalia without powering up the Scourge Regalia form. Undeterred, Ryuko keeps on attacking, forcing Ira to bring out Scourge Regalia's full power, attempting to forcefully mold Ryuko into a model student. However, Senketsu sets a plan into motion by pulling Ryuko out of her synchronized mode, allow her to use Senketsu's fangs to break into Ira's uniform and destroy it from the inside using a new form, Senketsu Senjin (鮮血閃刃?, Senketsu Blade Flash), winning the match. With Ira defeated, Ryuko prepares to face up against her next opponent, Houka Inumuta.