Kamijou Touma is a student living in Academy City, a highly advanced place in terms of technology. Despite being gauged as a level zero esper (no powers), he possesses on his right hand the Imagine Breaker, an ability that negates any power whatsoever. Touma finds a young girl named Index who is trying to run away from Necessarius, a powerful magic organization that she is member of. Blessed with the skill of memorizing any sort of information, she holds 103,000 forbidden magical books within her head. As science and magic cross paths, Touma must face several dangers amid espers and magicians who appear at the exciting scientific town.
Index is still a fugitive and many powerful magical organizations and individuals want to take her to use the books in her memory, eliminating her in the process. War between those organizations is also starting to emerge. Index can only rely on her friend Tōma, who has always protected her, along with Misaka and other friends from the Academy.