Some time between the Meiji and Taisho period... A mother and son walk through heavy rain. The son, YOKI, sees strange, iridescent creatures float from the mountainside and then disappear. He does not yet know such creatures are called "Mushi" and can not be seen by ordinary men. Suddenly, there is a landslide and Yoki's mother is swallowed by the flood. A Mushishi woman named NUI finds the child, who miraculously survived, and takes him home with her...

Some years later, we meet Yoki again as an adult. Having lost his memory in an incident he can not recall, he is now called "GINKO." He is a "Mushishi," one who studies the Mushi he could see as a child and protects ordinary men from the illnesses that they inflict. He travels alone through the thick mountain snow, looking for a night's lodging. We see that his hair is white like the snow and one of his eyes is now missing...

Ginko makes his way to a house where a young woman named TANYU has fallen ill. Born to a family with a strong connection to Mushi, Tanyu records the ancient stories of the Mushi onto scrolls. She fell ill after she heard a tale from a blind Mushishi woman. The woman told her about how she had fought off a powerful Mushi called "Tokoyami," which lived at the bottom of a pond, and about an eyeless fish which lived at the bottom of the Tokoyami called "Ginko." Her extended exposure to the pond turned her hair white and took her eyes...

In the basement library of Tanyu's house, Ginko reads the scroll containing the tale of the blind Mushishi woman. It sounds strangely familiar to him, as if he has heard the story before... the story of a boy named "Yoki," the sole survivor of a landslide...