|Set several years after "The Great Uprising", a future geological phenomenon in the Kanagawa Prefecture near Tokyo, people have developed a power granting them the ability to deconstruct, reshape, and crystallize matter at a molecular level using only thought and willpower. These people have come to be known as "Alter" users. With only 1% of the newborn generations receiving such special power, though this number rises steadily as the series progresses, some feel a superiority over normal humans.
There are two opposing forces of alters: the Native Alters, a group of Alter users who live outside the central city and avoid any relationships with the government; and HOLY, an organization of Alter users that are a subgroup of an organization called HOLD. HOLD functions as the Mainland government's super police force of the Lost Ground, while HOLY, composed exclusively of Alter users, serves as the "special operations" group, aiding HOLD in performing dangerous missions that might require the help of an Alter user.
Kazuma (dubbed "The Treasoner" in the manga and "The Shell Bullet" in the anime) and Ryuhou are the two s-CRY-ed characters bearing a rivalry used to drive and focus the plot. They spend much of the series trying to defeat each other, even when they are forced to work together. Neither can forget their bitter rivalry.
There is also a narrator, Kanami. Kanami is a close friend of Kazuma, who protects her and treats her like a little sister. She narrates the series with her dreams, unknowingly using her alter power to "scry" the emotions of the people she feels closely about. Her ability to peer into the emotions of the main characters is used frequently throughout the series to bring insight to the characters, and to tease viewers during previews for the next episode.
The series progresses through the initial introduction of the Alter power to a wider understanding of the politics and reason for "The Great Uprising". Each episode showcases a new Alter user, and his/her Alter, or a growth of the Alter of a previously introduced character. "The Great Uprising" is later revealed to be caused by a similar event in a parallel universe where all creatures are independent thinking Alters. During one of Ryuhou and Kazuma's battles, they open a gateway to the parallel universe, causing another uprising and attracting the attention of the Mainland government. The Mainland sends its agent, Kyouji Mujo, to the Lost Ground in an attempt to exploit the power of the parallel universe for economic gain. Mujo develops delusions of grandeur after becoming the defacto head of the Lost Ground government and absorbing the crystal entity from "the other side" to add to his already formidable Alter power. Both he and the crystal entity are defeated by the separate efforts of Kazuma and Ryuhou, respectively. The Mainland once again attempts to exert control over the Lost Ground by sending in a fleet of refined Alter users under their control, but they are defeated by Kazuma and Ryuhou.
After defeating the Mainland forces, Kazuma and Ryuhou engage in one final battle to settle their rivalry. After exhausting themselves to the point that they are too weak to maintain their Alters (and indeed, barely able to stand), they fight on with their bare hands till neither can move. In the next scene, a silhouetted hand is raised by the victor, the hand makes the symbol of the Zetsuei and then curls into a fist the same way Kazuma does when summoning his Alter. An epilogue, taking place years later, Kazuma and Ryuho remain the protectors of the Lost Ground, defending it from Mainland invaders. An older Kanami, who now has full control over her alter, awaits their return.