3X3 Eyes is the story of a young man named Yakumo Fuuji, who through a strange series of events becomes the immortal slave of the last of a race of 3 Eyed demons. The demon absorbs his soul to save his life, making him immortal in the process. Now, he begins a journey with the female demon in an attempt to find a way of becoming human. Of course, there are many complications along the way, not the least of which being that the demon is a female with a split personality, one achingly cute and the other being no-nonsense destructive power, and the romances that develop between.

Yakumo has trained and searched for 4 years, following Pai's mysterious disappearance. However, when he finally finds her, not all is well as her memory seems to be gone. They attempt to return her memory by going to the Holy Land, birthplace of the immortal race of Sanjiyans.