In a time where Japanese gods and demons walked the earth as giant beasts, Prince Ashitaka of the Imishi People, is sent from his home because of an incurable curse. He has heard, though, of the Forest Spirit, who can heal as well as take life. He sets out "to see with eyes unclouded by hate" to find a cure before the curse takes over and kills him. He discovers Iron Town, a peaceful village with mysterious origins, managed by Lady Iboshi, a woman with a war-like mind. The town is beset by the Wolf tribe, who has raised Mononoke, Princess of the Spirits, as their own.
Ashitaka is swept into a war between beast and man - a fight to save the forests, and to destroy them. Meanwhile, Humans have begun to fight amongst themselves to gain power and status. It is the displaced prince's duty to choose a side...but which is the right side?