Academy City, Japan, is at the forefront of science. Besides being 30 years ahead of the world technologically, more than three-fourths of this peculiar city's population consists of students developing their psychic abilities as espers in various institutions. Among these students is Touma Kamijou, a high school boy with the lowest psychic rank of zero, but with a mysterious power no scientist can understand: Imagine Breaker, which allows him to negate other supernatural abilities. This, however, doesn't affect Kamijou's life in the least as he plays his role as a regular teenager; that is, until he meets the strange Index Librorum Prohibitorum, a young girl who has memorized the entirety of the forbidden grimoires, and now a dangerous organization is hunting Index down. With several magicians looking to harm the girl, Kamijou will defend his new companion at all costs as he discovers a strange new realm of the supernatural.

Throughout history, an elite group of shrine maidens known as Toji have saved the world from Aratama, strange and malevolent beings bent on destroying humanity. In modern times, these warriors have been assigned to a special police squad to exterminate Aratama. The government has also set up five elite schools across the country to provide young girls the necessary sword fighting skills to eradicate these monsters and eventually join their fellow Toji in protecting the world. A student of one of those five schools, Kanami Etou is chosen to represent Minoseki Academy in a sword fighting tournament, where she meets the mysterious Hiyori Juujou. Although Kanami and Hiyori rise to the top of the tournament, their battle takes an unexpected turn, throwing the world of the Toji into chaos. Likely that the Toji are facing betrayal from within, the two are forced to flee the tournament, clashing with former comrades on the way.

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...

Touma Kamijou can't catch a break. After the invasion of Academy City, political tensions continue to rise as both the science and magic factions collide head on. It appears that Academy City intends to declare war against the Roman Catholic Church, consequently plunging the whole world into global warfare. Touma soon finds himself on the front lines once again, striving to protect his friends and allies. Toaru Majutsu no Index III serves as the last installment of the original franchise as Touma, Accelerator, and the true Level 0 Shiage Hamazura continue their separate journeys, leading up to the final act of the original light novel series.