While hunting in the Mesoamerican rainforest, Jaguar Paw, his father Flint Sky, and their fellow tribesmen encounter a procession of refugees fleeing warfare. The group’s leader explains that their lands were ravaged and they seek a new beginning. He asks for permission to pass through the jungle. Flint Sky comments to his son that the visitors were sick with fear and urges him to never allow fear to infect him.

At sunrise the next morning, the tribe’s village is raided by a group led by Zero Wolf. Huts are set on fire, many villagers are killed, and the rest of the adults are taken captive. Jaguar Paw nearly kills the sadistic raider Middle Eye, who kills the captive Flint Sky in retaliation and names Jaguar Paw “Almost”. Jaguar Paw’s heavily pregnant wife Seven and their young son Turtles Run escape by hiding in a small natural pit cave that also serves as a water reservoir, but are left trapped when Jaguar Paw is captured. The raiders then lead the captives on a long forced march through the jungle, leaving the children behind to fend for themselves.

On the journey, Cocoa Leaf, a badly wounded captive, is killed by Middle Eye, eliciting anger from Zero Wolf, who threatens his fellow raider with death if he kills another captive without permission. As the party approaches the Mayan city from which the raiders come, they encounter razed forests and failed maize crops, along with villages decimated by an unknown disease. A little girl infected with the illness prophesies Zero Wolf’s death and the end of the Mayan world. Once the raiders and captives reach the city the females are sold as slaves while the males are escorted to the top of a step pyramid to be sacrificed before the Mayan King and Queen.

As a result of a solar eclipse and the superstitions surrounding it, Jaguar Paw and the remaining captives are spared from being sacrificed. Instead, they are taken to be used as target practice by Zero Wolf and his men, and offered their freedom if they can run to safety before being killed. Jaguar Paw is injured but kills Zero Wolf’s son Cut Rock, and escapes into the jungle. Zero Wolf and eight of his comrades chase after him in vengeance. Back in his native jungle, Jaguar Paw now has the advantage and taunts his pursuers. Most of the hunters—including Zero Wolf and Middle Eye—are gradually killed off via natural hazards and traps laid out by Jaguar Paw, until there are only two left.

The drought breaks and heavy rain begins to fall, threatening to drown Jaguar Paw’s family, who are still trapped in the pit cave despite their attempts to escape. Seven gives birth to another son, who is born into the now dangerously rising water. Meanwhile, the two remaining raiders chase Jaguar Paw out of the undergrowth towards the coast. As they reach the beach, all three are stopped in their tracks by the sight of conquistador ships anchored off the coast and Spaniards making their way ashore, holding up a large cross. Jaguar Paw flees while the two raiders remain, seemingly mesmerized at the conquerors’ presence. Jaguar Paw returns in time to save his family from the flooded pit and is overjoyed at the sight of his new baby son.

Sometime later, as the reunited family looks out over the water at the Spanish ships, Jaguar Paw decides not to risk approaching the conquerors, insisting his family head back into the jungle. They depart in search of a new home and a new beginning.