In the aftermath of a fierce battle at Sekigahara in 1600, two legendary swordsmen, Kyoushirou Mibu and 'Demon Eyes' Kyou, faced off until a meteor disrupted their clash, causing them to disappear. Samurai Deeper Kyou picks up four years later, following Yuya Shiina, a gun-toting bounty hunter pursuing Kyoushirou, now a quirky, debt-ridden healer. Their journey is marred by an attack from a monstrous being seeking Kyoushirou's demise, triggering the awakening of 'Demon Eyes' Kyou trapped within Kyoushirou. Thus unfolds a grand saga delving into the secrets of these enigmatic swordsmen.