- Index Arc: Inojin Yamanaka is a Level 0 esper student at the science-centered Academy City, which is secretly run by the former magician, Rau Le Creuset. After with an encounter with the nun Hibari, Inojin learns that his Imagine Breaker power, capable of negating esper powers, works on magic as well. Inojin is able to prevent Hibari's memories from being erased (while losing his in the process), earning the friendship of Jean Kirschtein and Ellen Mira Mathers, a fire-wielding sorcerer and swordwoman respectively who are members of Necessarius, which is run by Archbishop Megumi "Nodame" Noda.
- Deep Blood Arc: The Alchemist Gintoki Sakata, a former guardian of Hibari, wishes to use the abilities of Nodoka Miyazaki in order to draw a vampire as part of a plan to save Hibari's life, not knowing Inojin has already done so.
- Sisters Arc: Inojin helps out with Makoto Nijima, the 3rd-ranked Level 5 esper who is trying to stop an experiment where Felicia, the many clone sisters of Makoto, are dying at the hands of the 1st-ranked Level 5 Katsuki Bakugo. Once Inojin defeats Bakugo, Makoto ends up developing feelings for Inojin.
- Angel Fall Arc: When someone invokes the spell Angel Fall, Inojin works with Ellen, and and surprisingly, his classmate Ghirahim, who turns out to be a double agent for both Academy City and Necessarius, to undo the spell. Inojin encounters Renka Ariake from the Russian Church, but it turns out the Angel Fall spell swapped her appearance with the Archangel Gabriel, who Ellen must now fight off.
- Three Stories Arc:
- Tsukune Aono is an Aztec magician who fears that Inojin is forming a powerful faction of espers and magicians, so he tries to cause a conflict between Inojin and Makoto.
- Bakugo, he finds himself becoming the protector of Filo, a child-clone of Makoto who oversees the surviving Felicias.
- Kirei Kotomine wants to find a grimoire in Hibari's mind in order to break a curse on his wife.
- Hyouka Kazakiri Arc: Hibari befriends Nagisa Momoe, who is in fact an Artificial Human derived from the collective esper powers. However, Liz Thompson, a Necessarius magician, wishes to kill Nagisa in order to spark a war between the magic and science sides.
- Orsola Aquinas Rescue Arc: Inojin and Necessarius teams up with a group of Roman Catholic battle nuns led by Shana in order to protect Sheryl Nome from being kidnapped by the Amakusa Catholics, led by Acnologia. Except it turns out that the Roman Catholics wish to to kill Sheryl for supposedly knowing how to decode a grimoire written by Rau Le Creuset that could lead to the end of Christianity, and the Amakusa wish to protect Sheryl from being killed.
- Remnant Arc: The surviving pieces of the Tree Diagram supercomputer, destroyed by Hibari during the first arc, become the center of a battle between esper teleporters Yuri Nakamura and Sayoko Shinozaki, the latter being Makoto's roommate.
- Daihasei Festival Arc: During Academy City's sports festival, Inojin, Jean, and Ghirahim team up to track down mercenary magician Shamal, who is working for Shampoo, a high ranking Roman Catholic official who wishes to bring Academy City under the church's control.
- Queen Of The Adriatic Sea Arc: Inojin and Hibari win a trip to Italy, only to learn that it puts them in position to stop another Roman Catholic plot. The Bishop Charles Zi Britannia plans to sacrifice Shana for her failures and in order to power a magical weapon to be used to destroy Academy City. Charles's defeat leads to God's Right Seat, a secret faction of the Catholic Church, to openly declare war on Academy City and Inojin.
- Academy City Invasion Arc: Yukari Tanizaki of God's Right Seat personally leads an invasion of Academy City. In response, the leadership has Filo abducted as part of the city's countermeasures, which turns Nagisa into an artificial angel whose aura is harmful to magicians. However, Felicia's abduction sparks a conflict between Bakugo and his former "mentor" Ali Al-Saachez, leading to the latter's death.
- Skill Out Uprising: Bakugo, Ghirahim, Tsukune, and Yuri are forced to become an underground black-ops team called GROUP. Their first mission is to stop a faction of Skill Out (delinquients with no esper powers) lead by All Might from rebelling. Once All Might is killed, the remaining Skill Outs are lead by Saito Hiraga. They are given a task by the city, in exchange for being left alone: kill Makoto's mother Sailor Jupiter, who was planning to take her daughter out due to the conflict between the city and the Catholic Church. The plot to kill Sailor Jupiter fails due to interference by Bakugo and Inojin.
- Document of Constantine Arc: The Catholic Church uses the Document of Constantine to get all its followers to protest Academy City. Therefore, Inojin and Ghirahim are sent to Avignon, where they meet with Mamako Oosuki, a member of the Amakusa Catholics. However, the Document is protected by another member of God's Right Seat, Jiraiya.
- Battle Royale Arc: GROUP gets involved with the ongoing conflicts beween the underground organizations of Academy City. The leader of SCHOOL, Ryo Hazuki happens to be the 2nd-Ranked Level 5 Esper and Bakugo's rival. Then there is ITEM, consisting of 4th-Ranked Level 5 Kallen Kouzuki, second-in-command Shinka Nibutani, Sensor Character Mikuru Natsuki, explosives expert Kaguya Yamai, and newly recruited lackey Saito. Kaguya ends up betraying ITEM, leading to Kallen killing her. Kallen tries to force Mikuru to use her abilities to track down Ryo, but Saito, who had developed feelings for Mikuru, realizes Mikuru is getting sick from overuse of her powers, causing him to rebel, and defeat Kallen, despite Saito being a powerless Level 0. As for Ryo, he has his confrontation with Bakugo, but he ends up being incapacitated once Bakugo figures out how to get around Ryo's powers.
- Acqua of the Back Arc: After Yukari's and Jiraiya's defeat, Nathan Drake of God's Right Seat threatens to personally come after Inojin. Mamako and the other Amakusa Catholics come to Academy City to serve as Inojin's protectors.
- British Royal Family Arc: Inojin and Hibari are called to the United Kingdom, where they meet the royal family, Queen Buzam A. "B.C." Calessa and her daughters, Ai, Semiramis and Inukai. However Semiramis is plotting a coup, hiring the magic cabal New Light (consisting of Yukio "Yukki" Hidaka, Elma, Kayoko Himeji, and Akiho Shinomoto) to acquire the Curtana Original. During the coup, Dio Brando, head of the Knights of England, effortlessly defeats Ellen, only in turn to be defeated by Nathan Drake, who came in time to rescue Ai. In the failed coup's aftermath Sephiroth, the last member of God's Right Seat and its leader, steals a magical device that gives him access to the 103,000 grimoires in Hibari's memory. He escapes to Russia, causing Inojin to chase after Sephiroth.
- DRAGON Arc: GROUP tries to uncover the secret to the codename DRAGON, only to learn that it refers to Roger Smith, a mysterious angel-like entity that Rau Le Creuset seeks to summon and previously sought guidance from. However, Roger's manifestation caused Filo to fall ill, which leads to Bakugo going to Russia for a cure. Also, Saito and Mikuru flee Academy City for Russia as well in order to escape a rampaging Kallen.
- World War III Arc: Inojin, Bakugo, and Saito's journeys leads them to the Elizalina Alliance of Independent Nations, which is lead by Noike Kamiki Jurai. Bakugo, however, finds himself forced to fight Edelgard von Hresvelg, an aged up clone of Makoto, sent to deal with him. Meanwhile, Sephiroth seeks to complete his plan, which includes abducting Renka and taking Inojin's right arm for himself.
Inojin and Hibari meet aspiring Idol Singer Kuroyukihime
, who seeks to sing for the opening of the city's new Space Elevator
. However Kuroyukihime is caught in the battle between Weiss Schnee
, member of Academy City's Black Crows, and a magician task-force (consisting of Erina Nakiri
, Mai Sakurajima
, and Kokone Kizuki
) lead by Jean. Not only that Shimakaze
, the woman behind the space elevator's construction, wishes to use the singer to power a spell that uses the space elevator as a focus, which would cause calamities over the entire planet, in a desperate attempt to undo her immortality.
- Level Upper Arc: Makoto works with Sayoko (who is rather open with her feelings for Makoto), Sayoko's partner in Judgment, Level 1 Yui Hirasawa, and Yui's classmate, Level 0 Mito Takami, to investigate a device that an increase an esper's powers with no effort. It turns out that the scientist Motoko Kusanagi is using Level Upper to connect its users to create a Hive Mind in order to tap into the newly created computing power.
- Sisters Arc: Makoto learns from Nene Konoe that Felicia, the 20,000 clones of Makoto, are being killed by Bakugo as part of an experiment to create a Level 6 esper. Makoto tries to halt the experiment by attacking associated facilities, which results in ITEM being sent after her.
- Daihasei Festival Arc: During Academy City's sports festival, Makoto learns that Asia Argento, a fellow Level 5 with mental powers, had Felicia 10032 abducted. However Asia was trying to protect Felicia 10032 from various forces after her, who turns out to be Professor Torbjörn, who wants to try making Makoto a Level 6 after failing with Bakugo, and Yume Nijino, who wants revenge on Academy City's leadership for the death of Chika Fujiwara, another Makoto clone. When Makoto is forced to undergo the process, Inojin teams up with Mikazuki Augus, the seventh-ranked Level 5 whose abilities seem to run on being Hot-Blooded, in order to stop her.
- Necromancer Arc: Bakugo, the top-ranked Esper of Academy City, and his ward Filo, unknowingly encounters magic when they run into the necromancer Hanayo Koizumi. As it turns out Mad Scientist Haruto Tokishima, who learned of necromancy techniques from Hanayo, is seeking the dying memories of the Felicia clones that Bakugo killed. Haruto is actually being manipulated by Shiroe, an ancestor of Hanayo who is possessing the body of Haruto's sister.