"A Certain Magical Index" is set in a world where science and magic coexist, often in conflict. The story primarily unfolds in Academy City, a technologically advanced metropolis where students develop supernatural abilities known as "esper powers." The narrative centers on Toma Kamijo, a high school student with the unique ability to nullify any supernatural power with his right hand, known as the "Imagine Breaker." Despite this ability, Toma is classified as a Level 0 esper, the lowest rank, making him an underdog in a city dominated by powerful espers.

The plot intertwines two major factions: the science side, represented by Academy City and its espers, and the magic side, consisting of various religious and magical organizations. Toma becomes entangled in the conflict between these factions after encountering Index Librorum Prohibitorum, a young girl who is a walking library of 103,000 forbidden magical texts. Index is pursued by magicians who seek to exploit her knowledge, and Toma vows to protect her, despite his lack of understanding of the magical world.

As the story progresses, Toma encounters numerous allies and adversaries from both the science and magic sides. Notable characters include Misaka Mikoto, a Level 5 electromaster known as "The Railgun," and Accelerator, the most powerful Level 5 esper, who initially serves as an antagonist. The narrative explores themes of morality, the consequences of power, and the clash between science and religion, often through intense battles and complex political intrigue.

The series is divided into multiple story arcs, each introducing new characters and expanding the world-building. Key arcs include the "Sisters Arc," which delves into the dark experiments involving Misaka Mikoto's clones, and the "Academy City Invasion Arc," where the city faces external threats from magical organizations. Throughout these arcs, Toma's resolve to protect his friends and uphold his ideals is tested, often placing him in direct opposition to powerful forces.

"A Certain Magical Index" blends action, mystery, and philosophical undertones, creating a rich narrative that explores the intersection of science and magic. The series is known for its intricate plotlines, diverse cast of characters, and the dynamic interplay between its two central factions.