As tensions between the world of magic and Academy City continues to rise, Touma Kamijou and his hand of negation must face off against both esper and magician in order to protect the lives of those around him. Of course, he is not alone in his fight; whether by his side or out of sight, allies and enemies both old and new will enter the fray to help him. Toaru Majutsu no Index II continues the story of action and comedy, as the scale of Touma and his allies' battle grows ever larger. A conflict is slowly brewing on the horizon, and magic and science will cross paths once again in the war to come.

Continuing after the Level Upper incident, another phenomenon torments Misaka. A phenomenon called Someone's Watching, its effect feels like the electricity in one's body flow backwards. With the help of her friends, Misaka fights against the unknown enemy.

In the scientifically advanced Academy City, a miracle is about to occur: the completion of the world's first space elevator, Endymion. Meanwhile, a certain high school student, Touma Kamijou, and his companion Index are going about their daily lives when they encounter and befriend Arisa Meigo, a cheerful and ambitious singer. When strange occurrences begin taking place throughout the city, they lead to the discovery of an intricate plot surrounding Arisa and Endymion. Things only get more complicated when the Stiyl Magnus appears, signifying that the magical world is somehow involved too...

Onmyoudou magic was once a powerful technique used by the Japanese during the second World War in order for them to gain the upper hand and establish their nation as a formidable force. But Japan was quickly defeated after the revered onmyouji Yakou Tsuchimikado caused the Great Spiritual Disaster, an event which plagues Tokyo to this very day. As a result of this mishap, the Onmyou Agency was established in order to exorcise further spiritual disasters and combat the demons that would make their way into the world. Now, Onmyoudou has become far more modern, simplified, and refined for use in a wide variety of applications such as medicine and technology. However, not everyone is able to utilize the magic, as is the case with Harutora, a member of the Tsuchimikado's branch family. Despite an old promise to protect Natsume, the heir of the Tsuchimikado's main family and Yakou's supposed reincarnation, as her familiar, Harutora has no talent and chooses to live a normal life instead. But when a prominent member of the Onmyou Agency attempts to recreate the same experiment which led to Japan's downfall, he decides to make good on his word and fight by Natsume's side.