Misaki Ayuzawa is a unique phenomenon within Seika High School. In a predominantly male institution, she became the first-ever female student council president through her honesty and diligence. Ever since Misaki got promoted to the position, she has been working tirelessly to ensure a better school life for all girls. Despite that, Misaki is very strict with the boys, which has earned her the title "Demon President." One day, after hearing a girl cry in the hallway, Misaki encounters Takumi Usui—the most popular boy in the school—as he rejects a love confession. Enraged at what she is seeing, Misaki reprimands him for making the girl cry. However, Usui is indifferent and brushes it off as nothing. Unexpectedly, Misaki soon runs into Usui again, but this time when she is working at a maid cafe! Embarrassed that someone has found out about her secret occupation, Misaki promises herself not to let Usui destroy her reputation. However, the mysterious boy now begins to visit the same cafe regularly to observe and tease Misaki. When push comes to shove, will Usui still be able to keep the president's secret?

It is 1983, and Hinamizawa is under quarantine. A mysterious and deadly virus has been discovered within the small village, and its residents—such as teenager Keiichi Maebara and his friends Mion Sonozaki and Rena Ryuuguu—are left confused and frightened by the situation. As the villagers begin to search for a way to stop the affliction from spreading, some make drastic plans, which leaves Keiichi and his friends looking for a way to escape the village. But when tensions reach an all-time high, some of his group may not make it out unscathed as they fight for their lives against enemies both seen and unseen.

The student-filled Academy City is at the forefront of scientific advancement and home to the esper development program. The seven "Level 5" espers are the most powerful in Academy City, and ranked third among them is middle schooler Mikoto Misaka, an electricity manipulator known as "The Railgun." When strange incidents begin occurring throughout the city, she finds each crime to be connected to the elusive "Level Upper," a legendary device that allegedly increases the esper level of its user. As the situation escalates, it becomes apparent that there is more to the Level Upper than meets the eye, and that Academy City may be a far more twisted place than the glamorous utopia it appears to be. Toaru Kagaku no Railgun focuses on Mikoto and her friends—and the dangerous situations they find themselves in—as they get caught up in the matter of the Level Upper. As Mikoto says, "There's never a dull moment in this city."