Created by Lady Sakuya, the Goddess of Attunement, "Samsara" is the endless cycle of death and rebirth between the worlds of Atoma—modern-day Earth—and Gulgraf, a fantasy-like land. Upon death, a soul is reincarnated into the other world with no memories of their past life.

An untimely plane crash in Atoma results in the death of middle school student Yachiyo Hitotose. But instead of being reborn, she awakens in Gulgraf—memories and body intact—and is proclaimed the reincarnation of Lady Sakuya. Plagued by vicious creatures known as "Blau," the people of Gulgraf rely on those who wield "Nidana," 12 pieces of Lady Sakuya's power which have been passed down through her followers' familial lines. Through the use of a keepsake from her mother, Yachiyo can temporarily fuse with Nidana holders, accessing the power known as "Nirvana."

However, with Yachiyo's arrival, foes who have awaited Lady Sakuya's return begin moving once again. Unable to turn her back on those in need, Yachiyo—accompanied by Nidana holder Mar Barae—sets out to unite the remaining Nidana holders in order to protect the people of Gulgraf.