Academy City is a highly developed place in terms of technology. It is said to be 20 to 30 years ahead of the rest of the world, and 80% of its 2.3 million residents are students. The focus of studies here is directed towards esper powers. Misaka Mikoto, one of the top level espers in town, shares a room with Kuroko Shirai, another high level esper who is a member of Judgement, a law enforcing agency composed of students. Both attend Tokiwadai, a private school reserved for the high-leveled and the rich. Kuroko's partner at Judgement, Kazari Uiharu, is a low level esper who studies at Sakugawa middle school. Her best friend and classmate there is Ruiko Saten, a level zero, one who has no esper powers. Together, the four encounter several adventures in the exciting scientific town.

木之本樱，是擅长体育的小学4年级学生。某天，小樱从学校回家，在平常都没有人的地下书房发现似乎有什么人的样子。小樱走下去一看，那里有一本闪耀着金色光芒的书。里面装有牌，然而，在读写在上面的文字的时候，刮来了剧烈的风，牌四处飞散开去。从书的最后，出现了名为可鲁贝洛斯的奇妙生物，书中写着“库洛牌的封印被解开之时，灾难就会降临世间”之类的话。随后，可鲁贝洛斯将封印的钥匙交给了小樱，令她成为收复牌的魔卡捕获者。当晚，小樱用魔法与实体化的魔卡对决……