The year is 1457. Princess Fuse, daughter of Yoshizane Satomi, Lord of Awa province, is forced into matrimony with her dog, Yatsufusa. This situation occurs when, under siege by the neighboring army of Lord Kagetsura Anzai and facing starvation. Yoshizane makes a desperate, last-ditch promise to the animal. Ultimately, the princess is killed, along with Yatsufusa, by a bullet from the gun of Daisuke Kanamari, who had come to rescue her. At the moment of Fuse's death, eight spirit beads from the necklace she was wearing disperse into the sky and the legend of the dog warriors begins.

The year is 1458. A child is born in the village of Otsuka, in Musashi Province. His name is Shino Inuzuka. After coming of age, he is entrusted with a legendary sword, the Murasame, by his father Bansaku. Shino's father, however, commits hara-kiri after losing face when his brother-in-law, Hikiroku Otsuka, tries to trick him into giving up the sword, Then Shino, devastated by his father's death, somehow comes into possession of a small bead, On this strange bead, the Chinese character ""KO"", symbolizing filial devotion mysteriously appears.

Sosuke becomes an assassin after being ordered by Kamezasa to kill Shino. The two warriors, however, soon realize the extent to which fate has connected them, and make a pledge of brotherhood. As for Hamaji, she learns that her hand in marriage has been promised to the jindai, Higami Kyuroku. Deeply in love with Shino and despondent over this news, Hamaji decides to kill herself, but is saved at the last minute by Samojiro Aboshi, who later reveals to her his true nature as an evil sorcerer and sets upon Hamaji himself. Hamaji's subsequent rescuer turns out to be her long lost brother, Dosetsu Inuyama, from whom she was separated at birth.

In the midst of the disturbance in Otsuka village caused by Hamaji's disappearance, there comes the arrival of evil itself, personified by the jindai and his retainer, to whom the village chief and his wife soon fall prey. Only one man, Sosuke, is able to stand up to them, though it is he who is ultimately arrested and blamed for the murders of his step-parents. Meanwhile. Shino arrives in Koga and is granted an audience with the Shogun, Nariuji Ashikaga. The legendary Murasame sword that he offers up, however, is revealed to be a fake, and Shino becomes a hunted criminal. But the man released from captivity in the castle dungeon and assigned to capture Shino turns out to be none other than the fourth dog warrior, Genpachi Inukai.

One day, in the town of Gyotoku, in the province of Shimousa, an innkeeper named Kobungo Inuta rescues two men while fishing on the Tone river. The men turn out to be Shino and Genpachi, who had been adrift since falling into the river from Horyu Tower. Kobungo's brother-in-law Fusahachi, however, recognizes the two as fugitives, and alerts the authorities. During the heat of an intense battle, Fusahachi mistakenly kills his wife, Nui, and in his moment of shock, he is struck down by Kobungo. But all that remain are the carcasses of two dogs...

Leaving Gyotoku, the three warriors take Nui's infant son Daihachi and set off for Otsuka village. Back in Otsuka, Sosuke faces a death sentence after being charged with the murders of his step-mother and father. After getting wind of this, Shino and Genpachi go to his rescue. Under cover of night, the two sneak onto the killing ground and hide themselves. Then, just as Sosuke is about to have his punishment of crucifixion carried out, they pounce... Will they succeed in their quest to rescue Sosuke and escape to safety?