In the 11th year of the Meiji Era, the end of the samurai shogunate and the prohibition of swords has left Japan with lasting scars. Displeased by these recent changes, many former samurai plot against the new government, inciting a wave of bloodshed. To counter this movement, the government constructs a colossal prison in the middle of Lake Biwa. Unofficially assigned to help the police arrest criminals, Tenka Kumou also serves as a ferryman to the Lake Biwa prison with the help of his two younger siblings: the ambitious Soramaru and the enthusiastic Chuutarou. Together with the former Fuma ninja Shirasu Kinjou, the Kumou brothers live a frugal and joyful life mostly dedicated to studying and training. However, behind this relatively uneventful daily routine, the specter of the Orochi curse is starting to spread its shadow over the city of Oumi. According to legend, every three hundred years, Orochi reincarnates in a human vessel—and it is believed that this is the harbinger of an imminent catastrophe. As various groups clash in search of Orochi's vessel, some aim to seal the curse, while others have darker plans in motion.

The greedy samurai lord Daigo Kagemitsu's land is dying, and he would do anything for power, even renounce Buddha and make a pact with demons. His prayers are answered by 12 demons who grant him the power he desires by aiding his prefecture's growth, but at a price. When Kagemitsu's first son is born, the boy has no limbs, no nose, no eyes, no ears, nor even skin—yet still, he lives. This child is disposed of in a river and forgotten. But as luck would have it, he is saved by a medicine man who provides him with prosthetics and weapons, allowing for him to survive and fend for himself. The boy lives and grows, and although he cannot see, hear, or feel anything, he must defeat the demons that took him as sacrifice. With the death of each one, he regains a part of himself that is rightfully his. For many years he wanders alone, until one day an orphan boy, Dororo, befriends him. The unlikely pair of castaways now fight for their survival and humanity in an unforgiving, demon-infested world.

To aid his conquest of Japan, the ruthless lord Daigo Kagemitsu offers to sacrifice his soon-to-be-born son to 48 demons. The demons accept, and the next day, the child is born with several missing limbs and is ruthlessly cast down a river. Fifteen years later, a stubborn young boy named Dororo struggles to survive against hunger and oppressive samurai on the streets of an impoverished and war-torn village. After angering a group of thugs, Dororo is attacked by them, but a mysterious man interrupts them, claiming to hear spirits nearby. Sure enough, a monster emerges from the river, and the man then removes his prosthetic arms, revealing blades hidden underneath, with which he slays the monster before leaving. That night, as the man walks through the forest, Dororo approaches him and declares that he will accompany him. From this, the man, Hyakkimaru, reveals that many of his body parts were stolen by demons and that though he sought a peaceful life, he couldn't escape their relentless onslaught. Despite the tale, Dororo still insists on tagging along. And thus, Hyakkimaru travels through Japan with his new companion and a puppy named Nota, facing the brutality of both hell and mankind.

Xiao Yan, the best Xiao family fighter ever. At the age of 4, he began his training, at 10 he already owned the ninth level of strength, and at 11 - the tenth, so he became the youngest fighter in the history of his family. But at the age of 12, something unpredictable happened: he lost almost all of his strength. For the next three years, neighbors mocked him and even broke off his engagement. It would seem that nothing will help him, but then a spirit appeared from his ring, which showed him the way to power. Xiao Yan again became a favorite of the family and the crowd, but this could not satisfy his ambition. To avenge the failed wedding, he goes to the mountains and, with the help of an old herbalist, becomes stronger and stronger.