Eyes of Fire is a Gothic Colonial film that takes place in the year 1750 on the American frontier during the colonial days, before the United States declared its independence. A group of pioneers narrowly escape persecution when their preacher is accused of adultery and polygamy. The preacher, Will Smythe, is accused of having an affair with a married woman, Eloise Dalton, whose husband is away hunting for food, and another woman, Leah, who is insane. Also among their group is Eloise’s daughter Fanny Dalton, the couple Jewell Buchanan and Margaret Buchanan along with their daughter Cathleen, Calvin and his wife who goes by the name Sister, and their granddaughter Meg.
As the group travels farther away from their town, the threat of attack from hostile Native American tribes becomes more prevalent until the group is eventually ambushed. Calvin does not survive the attack, but the others are protected by Leah, who has used witchcraft to provide their protection. All the while the others are unaware that Leah is using magic to keep them safe. The remaining members of the group are forced to abandon their trail along the riverbank, and take cover in the woods far from man-made trails. At this time, Eloise’s husband Marion Dalton returns home to find news that his wife was scheduled to be executed along with Will for affair and also learns that the two are on the run with others from the town. Marion pursues and eventually catches up to them. Leah wanders away from the group for a short while.
By this time the Shawnee Indians have caught up to the group and Marion Dalton, who speaks fluently in many tribal languages, is able to convince the Shawnee to abort the attack, at least for a short while, though Marion is certain the Shawnee will be back in bigger numbers. Leah returns covered in white feathers and Marion recognizes this as a warning from the Shawnee Indians to other members of the Shawnee tribe not to enter a nearby valley. Realizing that the Shawnee have superstitions about the valley, Marion leads the group into the valley, knowing that if the Shawnee were to return, they would not follow the pioneers into the valley because of various Native American superstitions some of the tribes have in regards to this particular valley.
Once the group settles in the deserted valley, they are safe from any and all tribes of Native Americans. Though the pioneers are no longer under the threat of attack from the Shawnee, they find a young Native American orphan on the outskirts of their camp. The pioneers are still unnerved by the previous attacks, but reluctantly bring the girl into the camp and care for her. It seems that only Will is pleased with the orphan’s unexpected appearance, and he is delighted at the possibility of baptizing her into Christianity. Aside from Will, it seems the others in the group are unnerved by the orphan girl’s presence. And Leah, who has an extraordinary connection to the supernatural, senses that there is something unusual about the Native American child, and Leah soon begins to have visions as she tries to uncover the motives of the orphan girl. Fanny disappears soon afterward, and her body is later found by Marion, with the help of Leah through her abilities and visions, though Fanny appears to be in a coma. Only when Fanny awakens do they realize that the warnings to stay away from the valley are founded on more than just mythology, coupled with the frightening revelation that the orphan girl is more than what she seems when the group is terrorized by an evil spirit that desires to make them all its living captives.