In 1719 in the Great Plains, Naru, a young Comanche woman trained as a healer, dreams of becoming a great hunter like her brother, Taabe. While tracking deer with her dog, Sarii, she witnesses the lights of an alien Predator's spacecraft, which she interprets as a Thunderbird, taking it as a sign to prove herself. At the village, one of their tribe's hunters has been taken by a mountain lion. Taabe says Naru can come on the search party, but only to help track the cougar and provide medical treatment if they find the hunter alive. They retrieve the wounded hunter and depart, though Taabe stays behind to find and kill the big cat. Finding large unusual tracks and a meticulously skinned rattlesnake, Naru circles back with Paake and finds Taabe. Together the three set a trap for the mountain lion but it kills Paake.

Naru faces off with the big cat on the branch of a tree but, after being distracted by the strange sounds and lights of the Predator in the distance, falls and strikes her head. She wakes up in her family home, having been carried back by Taabe. He later returns to the village carrying the dead mountain lion, earning him the title of War Chief. Convinced of a greater threat they've never seen before, Naru departs with Sarii. She comes across a herd of skinned bison left to rot on the plains; baffled by the wasteful slaughter, she says a prayer for their spirits. Eventually, she stumbles into a mud-filled bog pit, which nearly swallows her before she escapes. Naru and Sarii are later attacked by a grizzly bear. As they flee for their lives, the bear is killed by the Predator, giving Naru time to escape before running into a group of Comanche sent to find her. The Predator ambushes and kills the men in combat, while Naru is caught in a foothold trap; the Predator leaves as it no longer sees her as a threat.