Mushishi begins with a tense moment as Yoki and his mother traverse through the mountains, when, unexpectedly, a cliff crumbles around them. This pivotal incident triggers a nonlinear storyline that oscillates between moments in the past and present. As the narrative unfolds through a series of flashbacks, we learn that Yoki is the sole survivor of the catastrophe and is subsequently taken in by Nui, a skilled Mushishi, or Bugmaster. Nui possesses a deep understanding of Mushi, ethereal bug-like entities that remain unseen by most humans. She resides beside a tranquil pond, home to two distinct types of Mushi: a fish-like creature known as Ginko, who inhabits the shadowy depth referred to as Tokoyami. The prolonged gaze Nui holds on the Ginko alters both one of her eyes and the color of her hair due to the influence of Tokoyami's shadow. Tragically, Nui eventually becomes engulfed by the Tokoyami, and during his attempt to rescue her, Yoki is also consumed. To escape this fate, he sacrifices one of his eyes along with fragments of his memory, subsequently adopting the name Ginko, as it is the only identity he can recollect.
As the story transitions to the present day, Ginko, caught in a ferocious blizzard, stumbles upon a village inn. Upon revealing himself as a Mushishi, he is sought out by the villagers who are experiencing mysterious hearing loss. After Ginko assists them, the innkeeper requests his help with her granddaughter, Maho, who suffers from deafness, visibily displays horns on her forehead, and hears peculiar sounds. The troubling aspect is that Maho's mother exhibited identical traits and had met a grim fate. However, Maho retains her mother's horns, discovering that they are a form of disguised Mushi responsible for her ailment. Demonstrating his expertise, Ginko cures the young girl before resuming his journey.
Ginko soon receives a letter from Tanyu, a woman ensnared by a Mushi compelling her to document the existence of Mushi to liberate herself from its grip. During his travels, he encounters Koro, another Mushishi on the hunt for a vibrant, rainbow-hued Mushi. Arriving at Tanyu's residence, her nanny, Tama, shares a harrowing account involving a mysterious white-haired woman who warned them about the Tokoyami. When Tanyu endeavored to record her experiences, she suffered from paralysis and gangrene as a result. Requesting permission to examine the writings on Tokoyami, Ginko notes how these very documents begin to animate, returning to Tanyu and worsening her condition.
In an intense confrontation, Ginko battles the Tokoyami within the writings warehouse, while Tama and Koro struggle to extract the creature through bloodletting. The newly healed Tanyu joins her allies at the warehouse, discovering Ginko collapsed on the ground. She endeavors to detach the writings from his being, reaffixing them to the parchment. With the writings successfully removed, Ginko revives and continues his journey alongside Koro. Their paths diverge as they ultimately discover the elusive rainbow-like Mushi. After their adventure, Koro returns to his homeland committed to constructing bridges. In a gripping finale, Ginko confronts a Tokoyami-infested Nui, carrying her to the ethereal River of Light, known as Koumyaku, a radiant stream teeming with luminous Mushi, believed to be the source of all Mushi life.
