Ichika Orimura is attending the Infinite Stratos Academy as he is the first male to ever pilot an IS where he becomes a sensation among the all female students of the academy. With his homeroom teacher being his older sister Chifuyu, an ex-IS pilot, Ichika is in unease and unprepared and trying to get use to the academy. Later he learns his dorm roommate is his childhood friend, kendo champion Houki Sinonono, who he has not seen in six years. When his class decides to elect him as their class representative, the British cadet representative and noble, Cecilia Alcott is against it and challenges him to an IS duel for the position.

Ichika is told by Chifuyu that he will be provided with his own personal IS for his match against Cecilia, a rarity since there are only 467 IS Cores that were created by Tabane Shinonono, Houki's older sister before she disappeared. To prepare himself, Houki agrees to train Ichika by practicing Kendo. On the day of the match, Ichika is given the IS Byakushiki against Cecilia's IS, Blue Tears. Cecilia has the advantage at the beginning as her IS is a Sniper while Ichika IS is a Close-range fighter but Ichika manages to transform his IS into First Shift, the IS second form and pulls out an energy sword. Just as Ichika is about to strike Cecilia, the match is declared over and Cecilia the winner because Ichika's energy sword completely depleted his IS shields. Despite losing, Ichika agrees to train more with Houki while Cecilia is unsure of herself despite winning the match.

Cecilia takes a liking with Ichika and gives the position of class representative to him instead much to Houki's chargin. The next day, Ichika meets Lingyin, the new transfer student from China who also happens to be his childhood friend and also the class representative of her class. After Ichika and Lingyin get reacquainted with each other, Cecilia and Houki get jealous and coached Ichika in IS practice very hard. Upon learning Houki is Ichika's roommate, Lingyin tries to get Houki to let her become his roommate instead which Houki refuses. But Lingyin later leaves in anger after Ichika doesn't figure out the childhood promise they made and wants to settle it in the Inter-Class IS Tournament. With his match against Lingyin and her Shenlong IS next, Ichika prepares himself.

Ichika and Lingyin battle in the Inter-Class IS Tournament but their match is interrupted when a mysterious IS attacks the arena. As Ichika and Lingyin hold off the IS so the audience can escape, they soon realize the IS is an unmanned drone due to it's machine-like behavior. Together with Cecilia, the three of them manage to defeat the IS but not before it injures Ichika. As Ichika recovers while Lingyin watches over him, Ichika wonders the promise he made with Lingyin had a different meaning which the latter quickly denies. Meanwhile, Chifuyu and Maya examines the defeated IS and confirms it is an unmanned IS drone with a unique IS Core that didn't come from the 467 confirmed Cores the world has which makes them question who made it.

Houki has been given her own room by Maya and leaves in anger when Ichika is being dense about it but makes him promise to go out with her should she win the grade level individuals tournament, which spreads into a rumor that the winner of the tournament gets a date with Ichika. At the same time, a transfer student, another male IS pilot from France named Charles Dunois, arrives much to the joy of the girls of the Academy due to Charles's Bishōnen looks and "interest" with Ichika, who also becomes his new roommate. While Ichika's class has IS practice with Lingyin's class, Chifuyu has Lingyin and Cecilia battle against Maya in a Rafale Revive IS, a 2nd generation IS made by Charles' father's corporation, which Maya easily defeats Lingyin and Cecilia's more advanced ISs. While Ichika is having lunch with Houki, Lingyin, Cecilia and Charles, the girls try to give Ichika their lunches which he enjoys Houki's the most and feeds some of it to her much to the other girls' anger.

After losing against him in a practice bout, Ichika has a training session with Charles, which is interrupted by Laura who wants to fight him, but refuses. On his way back, he spots Laura talking with Chifuyu, begging her to return to Germany and that the IS Academy doesn't deserve her, but the latter doesn't listen. It is revealed when Ichika was kidnapped during the 2nd Mondo Grosso IS championship, Chifuyu forfeit the finals in order to rescue him. Upon returning to his dorm, Ichika walks in on Charles in the shower to discover he is actually a girl. Charles reveals she is her father's illegitimate daughter who was taken in after her mother passed away and made an IS test pilot. But when the Dunois corporation entered a financial crisis due to the demand for third generation ISs, Charles was ordered to act as a boy to give the company publicity and steal data from Ichika.

Houki becomes pressured to win the upcoming inter-class tournament after her attempt to ask Ichika out escalated into a rumor that whoever wins the tournament gets to date him. As Cecilia and Lingyin prepare to spar, Laura appears and goads them into a two-on-one battle, effortlessly countering all their attacks. When she continues to beat them at the risk of their lives, Ichika and Charles step in to rescue them before Chifuyu puts a stop to the battle, declaring it will be settled in the inter-class tournament. It is soon announced that the tournament will be conducted in pairs, with Ichika choosing Charles as his partner. On the day of the inter-class tournament, it is decided via lottery that Houki is to be paired with Laura against Ichika and Charles.

The match between Ichika and Charles against Laura and Houki begins where Laura focuses on fighting Ichika and pays no heed to her partner Houki, who is soon knocked out by Charles. Ichika and Charles uses their teamwork to take advantage of Laura's AIC shield to defeat her despite Ichika's shields running low after using Yukihira. With her defeat imminent, Laura reminisce her past of being a failed genetically engineered soldier unable to adapt an IS until meeting her teacher and role model Chifuyu but hates Ichika upon learning Chifuyu shows her softer side because of him. Not wanting to give up, Laura goes berserk which transforms her IS into a large, dark IS. Wanting to stop her, Charles gives her remaining IS power to Ichika to manifest Yukihira and uses it to strike the dark IS and free Laura.

Houki calls her sister, Tabane, who reveals she has completed an IS called Akatsubaki just for her. After being hassled in the morning by Laura, Ichika goes with Charlotte to the mall to buy swimsuits for their beach study session while Lingyin, Cecelia and Laura stalks them. When Charlotte notices them following her, she hides with Ichika in the dressing room to show off her swimsuit, but they are both discovered by Chifuyu and Maya. During the beach study session, the girls try to get close with Ichika with various results. As sunset arrives, Chifuyu talks with Houki about Tabane and believes her sister will come with the Akatsubaki IS on July 7.

After catching the girls listening at their room while Ichika is massaging her, Chifuyu has a talk with the girls about their feelings for her brother and gives them some advice. The next day, Tabane arrives to personally deliver to Houki the Akatsubaki, a fourth generation model with abilities far more advanced than the others. However, Chifuyu soon receives news that an an unmanned IS called the Silver Gospel has gone out of control. After assessing the situation, Chifuyu orders the group to stop it, while Ichika and Houki will pursue it, as only they would be fast enough to catch up with the Silver Gospel.

As Ichika and Houki begin their operation, the others notice how happy Houki looks, which prompts Chifuyu to tell Ichika to watch over her carefully. As Ichika and Houki engages in battle with the Silver Gospel and is about to corner it, Ichika notices an illegal fishing boat in the area and breaks off formation to protect it. Houki is angry at Ichika for ruining the plan but he scolds her for disregarding the boat's safety, which is something she never does. However, the Silver Gospel launches a surprise attack on them, which forces Ichika to shield himself to protect Houki. As the critically injured Ichika is admitted, Houki blames herself on what happened and wants to quit being an IS pilot but Cecilia, Lingyin, Charlotte, and Laura manages to convince her otherwise. Together, they decide to defy Chifuyu's orders to stand by and go after the Silver Gospel themselves.

While the girls fight Silver Gospel, Ichika has a dream where he meets a young girl and a warrior woman who asks him if he wants strength, which he agrees as he wants to protect his comrades. As the battle continues to rage, Houki manages to cut one of Gospel's wings and sees it fall into the ocean, only for it to re-emerge in its Second Shift form with "angel wings" and proceeds to to take down Houki and the rest. Houki is soon awakened by Ichika, who is now in Byakushiki's Second Shift form, Byakushiki Setsura, and gives Houki a hair ribbon as a gift as he still remembers July 7th as her birthday. With their combined strengths, Ichika and the girls finally defeat Gospel, with Ichika giving it the finishing blow. As they return back to their hotel, Chifuyu scolds them for defying orders but allows them some R&R as a reward for stopping Gospel.

On a hot day of summer vacation, Charlotte's plan to spend some time alone with Ichika at his house is somewhat ruined when Cecilia gets the same idea, later followed by Houki, Lingyin and Laura. They spend the afternoon playing games and making meals together. The next day, Houki helps out at a summer festival being held at her family's shrine and is surprised when Ichika shows up. Her time alone with Ichika, though, is soon ruined by the appearance of Ran Gotanda, who momentarily has gotten separated by her brother Dan Gotanda. Later, Houki attempts to confess her feelings to Ichika, but is instead drowned out by the fireworks.

Music video included in the Season 2 Bluray set. Contains both live concert footage and scenes from the anime.

An extended version of the second season's first episode, which is under the same title.

A program called "World Purge" sends illusions to all the girls about their ideal fantasies.

Picture drama included on the IS: Infinite Stratos 2 Blu-ray box.