A disgraced former executioner of the Shogun, Ogami Itto, wanders the countryside of feudal Japan with his young son, Daigoro, pushed in a baby cart that hides an arsenal of weapons. Having chosen the demon’s road of Meifumado, they survive as hired assassins while seeking revenge against the Yagyu clan, who murdered Itto’s wife and framed him for treason.

The second chapter of their journey finds Itto accepting a contract from a clan of indigo dyers. A traitorous clan official plans to sell their secret dye-making process to the Shogunate, which would ruin the clan, so Itto is hired to ensure the man never reaches the capital city of Edo. However, the turncoat travels under the protection of three fearsome warriors known as the Gods of Death: the Hidari brothers, each a master of a unique and brutal weapon.

Simultaneously, the Shadow Yagyu clan deploys a new weapon against the Lone Wolf. They dispatch Sayaka, the leader of their elite squad of female ninja assassins, to eliminate Itto and his son. Sayaka’s forces attack relentlessly, disguising themselves as acrobats, street performers, and even farmers, forcing Itto into a series of violent confrontations. Though wounded in battle, Itto dispatches the female ninjas one by one. The conflict takes a toll, and at one point Itto collapses from exhaustion, forcing the three-year-old Daigoro to nurse his father back to health by carrying water in his mouth and stealing rice cakes from a shrine.

Sayaka and her remaining spies eventually capture Daigoro, suspending him over a deep well to force Itto to drop his sword. Itto refuses to yield, and Daigoro, understanding their grim path, drops his own sandal to help his father gauge the distance. Itto rescues his son, and Sayaka, witnessing the unbreakable bond between father and child, retreats without a fight.

The paths of Itto and the Hidari brothers converge on a ship. When the vessel is set ablaze by a rival clan member, Itto escapes into the sea with Daigoro and the floating cart. Sayaka follows, attempting to kill them in the water, but is easily disarmed. As the three struggle in the cold water, Itto tears off their wet clothes and presses their bodies together for warmth, holding his son between them, an act that leaves Sayaka disarmed emotionally as well as physically.

The final confrontation takes place on a vast expanse of sand dunes. After the Hidari brothers massacre a squad of warriors hidden beneath the sand, Itto descends upon them. In a series of swift, bloody sword strokes, he kills the three masters of death one by one, culminating in a legendary cut that sprays blood in a fine mist, a sound known as the "howling of the wind." He then approaches the palanquin holding the traitorous official and finishes his contract.

As Itto pushes the cart along a coastal trail, he senses Sayaka following him, still holding a sword. He stops the cart, extends his blade behind him, and waits. After a long moment, he hears the sound of her katana drop to the ground, acknowledging that she can never defeat the Shogun’s former executioner. Without turning around, Itto continues down the road with Daigoro.