Humans live in the world of Assiah, demons in Gehenna. The two dimensions are not meant to interfere with each other, but demons still possess creatures in Assiah in spite of this. The humans who can fight these demons are known as exorcists. Rin Okumura is a boy who bears the curse of being Satan's illegitimate son. His foster father sacrificed himself to save him from demons. To avenge his foster father's death as well as to prove himself, Rin decides to follow the path of an exorcist.
Mistarcia is a magical world where humans, gods, and demons mingle together. In the past, the black-and-silver winged Bahamut has threatened to destroy the land, but humans, gods, and demons overcame their differences to fight together and seal its power. The key to that seal was split in two, one half given to the gods and the other to demons, so that they would never be united and Bahamut never released. Now, two thousand years later, the world is in an era of peace - until the day a woman steals the gods' half of the key.
In 2012, the world allegedly comes to an end at the hands of a human-made virus, ravaging the global populace and leaving only children untouched. It is at this time that vampires emerge from the recesses of the earth, likely followed by age-old horrors of the dark thought only to be myth. The vampires sweep the earth and claim it in a single violent stroke, subjugating the remnants of humanity and leading them beneath the surface to safety. This "protection" comes at the price of donating blood to their captors. At the age of twelve, Yūichirō and his friend and fellow orphan Mikaela plotted to escape along with the children in Hyakuya Orphanage. However, this resulted in their deaths and Mikaela sacrifices himself in order for Yūichirō to escape and be saved by members of the Moon Demon Company, an extermination unit of the Japanese Imperial Demon Army. Four years later, Yūichirō dedicates his life to destroy vampires and seek revenge against them for murdering his "family".
"The fourth true ancestor" is a legendarily strong vampire that shouldn't exist. Accompanied by the 12 "gun-beasts," this phantom vampire is said to have appeared in Japan. In order to find and kill this "fourth true ancestor," the government and the Lion King Organization order the dispatch of attack mages called "sword-maidens." For some reason an apprentice named Yukina Himeragi was chosen for the task. Wielding the strongest spiritual spear, Yukina comes to the special demon district Itokami City. There she encounters Kojou Akatsuki and learns the true nature of the "fourth true ancestor."
In another dimension the Devil King Sadao is only one step away from conquering the world when he is beaten by Hero Emilia and forced to drift to the other world: modern-day Tokyo. As "conquering the world" are the only skills the Devil King possesses - and are obviously unnecessary in his new situation - he must work as a freeter to pay for his living expenses.
Basara Tojo met his two cute little sisters, Mio Naruse and Maria Naruse. The two sisters revealed themselves as a member of the demon clan and Basara as a member of hero clan, demon clan's enemy, and is not related by family. Mio is the future Demon Lord and since Mio's power is not fully awakened, Basara will protect her from the demons who are after the power she inherited from her deceased father, Demon Lord Wilbert.
While cleaning out his family's Shinto temple, middle-school student Ushio Aotsuki stumbles upon a hidden cellar which houses a dangerous yokai. The yokai, pinned by a legendary weapon called the Beast Spear for 500 years, attracts many other supernatural creatures to the premises. Ushio is forced to free the creature – whom he names “Tora” – in return for his help in defeating them. Tora, who wishes to eat Ushio but is stalled by the Beast Spear, begins to haunt the boy in the hopes that an opportunity will present itself. However, Ushio's possession of the Spear seems to result in trouble after trouble, and Tora finds himself an unwilling ally to Ushio in his battles against various supernatural foes. Meanwhile, a greater danger lurks in the form of Hakumen no Mono, an incredibly powerful yokai with a thirst for destruction who is about to awaken from an extended slumber.