During Koyomi Araragi's second year at Naoetsu Private High School, he has a chance encounter with Tsubasa Hanekawa, the top honor student in his class. When they strike up a conversation, Hanekawa mentions a shocking rumor: a vampire with beautiful blonde hair and freezing cold eyes has been seen lurking around town. Happy to have made a new friend, Araragi writes off the rumor and goes about the rest of his evening in a carefree manner. However, on his way home, he stumbles across splatters of blood leading down the stairs to the subway. His curiosity pushes him to investigate further, so he follows the gruesome pools into the depths of the station. When he arrives at the source of the blood, he is terrified by what he sees—the rumored blonde vampire herself, completely dismembered. After she calls for his help, Araragi must make a decision, one which carries the potential to change his life forever.

Hole—a dark, decrepit, and disorderly district where the strong prey on the weak and death is an ordinary occurrence—is all but befitting of the name given to it. A realm separated from law and ethics, it is a testing ground to the magic users who dominate it. As a race occupying the highest rungs of their society, the magic users think of the denizens of Hole as no more than insects. Murdered, mutilated, and made experiments without a second thought, the powerless Hole dwellers litter the halls of Hole's hospital on a daily basis. Possessing free access to and from the cesspool, and with little challenge to their authority, the magic users appear indomitable to most—aside for a few. Caiman, more reptile than man, is one such individual. He hunts them on a heedless quest for answers with only a trusted pair of bayonets and his immunity to magic. Cursed by his appearance and tormented by nightmares, magic users are his only clue to restoring his life to normal. With his biggest obstacle being his stomach, his female companion Nikaidou, who runs the restaurant Hungry Bug, is his greatest ally.

The world of dreams can be an incredible window into the psyche, showing one's deepest desires, aspirations, and repressed memories. One hopeful tech lab has been developing the DC Mini, a device with the power to delve into the dreams of others. Atsuko Chiba and Kosaku Tokita have been tirelessly working to develop this technology with the hopes of using it to deeply explore patients' minds and help cure them of their psychological disorders. However, having access to the deepest corners of a person's mind comes with a tremendous responsibility. In the wrong hands, the DC Mini could be used as a form of psychological terrorism and cause mental breakdowns in the minds of targets. When this technology is stolen and people around them start acting strangely, Atsuko and Kosaku know they have a serious problem on their hands. Enlisting the help of Officer Konakawa, who has been receiving this experimental therapy, they search both the real and dream worlds for their mental terrorist.

In the town of Kamisu 66, 12-year-old Saki Watanabe has just awakened to her psychic powers and is relieved to rejoin her friends—the mischievous Satoru Asahina, the shy Mamoru Itou, the cheerful Maria Akizuki, and Shun Aonuma, a mysterious boy whom Saki admires—at Sage Academy, a special school for psychics. However, unease looms as Saki begins to question the fate of those unable to awaken to their powers, and the children begin to get involved with secretive matters such as the rumored Tainted Cats said to abduct children. Shinsekai yori tells the unique coming-of-age story of Saki and her friends as they journey to grow into their roles in the supposed utopia. Accepting these roles, however, might not come easy when faced with the dark and shocking truths of society, and the impending havoc born from the new world.