Nausicaä is the princess of the Valley of the Wind, a state on the periphery of what was once known as Eftal, a kingdom destroyed by the Sea of Corruption 300 years before the story begins. The leaders of the Periphery states are now vassals to the Torumekian Emperor and are obliged to send their forces to help when he decides to invade the neighboring Dorok lands. The Torumekians have a strong conventional military, but the Doroks have developed a genetically modified version of a mould from the Sea of Corruption to overwhelm the invaders. But when the Doroks introduce this mould into battle, its multiplication and mutation result in a "daikaisho" which floods across the land and draws the insects into the battle, killing as many Doroks as it does Torumekians. In doing so, the Sea of Corruption spreads across most of the Dorok nation, uprooting or killing vast numbers of civilians and rendering most of the land uninhabitable.
The Ohmu and other forest insects respond to this development and sacrifice themselves to pacify the rampant mould. However, the fact that the fungus can be manipulated and used as a weapon disturbs Nausicaä. Her trips into the forest have already taught her that the Sea of Corruption is actually purifying the polluted land. The Forest People, humans who have learned to live in harmony with the Sea of Corruption, confirm this is the purpose of the Sea of Corruption and show Nausicaä a vision of the restored Earth at the centre of the forest. Making friends of her enemies, Nausicaä travels deeper into Dorok territory to seek those responsible for manipulating the fungus, recruiting a God Warrior found in Pejite to muscle past both the Torumekian and Dorok armies.
Despite the loss of some of her companions, she is eventually able to reach Shuwa, the Holy City of the Doroks, and enters the Crypt, a giant monolithic construct from before the Seven Days of Fire. Nausicaä learns that the last scientists of the industrial era had foreseen the end of their civilisation. They created the mould and the Sea of Corruption to clean the land, altered human genes to cope with the pollution, stored their own personalities inside the Crypt, and waited for the day when they could re-emerge. However, their continual manipulation of the population is at odds with Nausicaä's belief in the natural order and has led to the cycles of violence which have plagued the world for a thousand years. She orders the God-Warrior to destroy its progenitors, giving humanity the opportunity to live or die without the benefit of the old society's technology.