In 1600, on the fog-shrouded battlefield of Sekigahara, two exemplary swordsmen engaged in a fierce duel. One was Kyoushirou Mibu, a noble and skilled warrior who possessed the unique powers of the Mibu Clan. The other was the thousand-man slayer known as "Demon Eyes" Kyou, distinguished by his blood-colored hair and eyes. Their legendary clash was abruptly ended when a meteor fell from the sky onto the battlefield, causing both combatants to vanish in its aftermath. Samurai Deeper Kyou begins four years later, when Yuya Shiina, a bounty hunter armed with a gun, tracks down Kyoushirou, who has become a perverted traveling medicine-man burdened by significant debt. While pursuing him to collect the bounty, they are attacked by an inhuman monster intent on devouring Kyoushirou. This encounter awakens "Demon Eyes" Kyou, whose consciousness had been trapped within Kyoushirou's body since that fateful battle. Thus begins a grand tale of these two legendary swordsmen and the uncovering of their secrets.