In the year 1600, an epic clash occurred in the misty battlefield of Sekigahara between two exceptional swordsmen. Kyoushirou Mibu, a noble warrior with unique abilities bestowed by the Mibu Clan, faced off against the notorious "Demon Eyes" Kyou, a crimson-eyed and haired slayer of thousands. However, the legendary showdown was disrupted when a meteor plummeted from the sky, causing both combatants to vanish upon impact. After four years have passed, Samurai Deeper Kyou starts with a gun-toting bounty hunter named Yuya Shiina trailing Kyoushirou, who has now become a lecherous and indebted traveling salesman. While en route, the duo is attacked by a monstrous creature intent on devouring Kyoushirou. Amidst the chaos, the consciousness of "Demon Eyes" Kyou, previously trapped inside Kyoushirou's body, emerges. The tale unfolds as the secrets behind these two swordsmen of lore are unraveled.