In 5000 BC, ten superpowered Eternals—Ajak, Sersi, Ikaris, Kingo, Sprite, Phastos, Makkari, Druig, Gilgamesh, and Thena—are sent by the Celestial Arishem to Earth on their starship, the Domo, to exterminate the invasive Deviants. The last Deviants are apparently killed in 1521, when the group's opinions differ over their continued relationship with humankind. Over the next five hundred years they mostly live apart, waiting for Arishem's orders.

In the present day, Sersi and Sprite live together in London. After Sersi's partner Ikaris left her centuries earlier, she is now in a relationship with human Dane Whitman who works at the Natural History Museum. When the trio are attacked by the Deviant Kro, Ikaris arrives and chases the creature away. The three Eternals travel to South Dakota to reunite with their leader, Ajak, only to find her dead. Sersi is posthumously chosen by Ajak as her successor, granting her the ability to communicate with Arishem.

Sersi learns that the mission of the Eternals was actually to prepare Earth for the Emergence. Arishem explains that, for millions of years, he has been planting the seeds of Celestials inside planets where the energy from large populations allows new Celestials to be born. The Deviants were sent to destroy the apex predators of each planet to ensure the development of intelligent life, but when the Deviants evolved and began hunting the planets' native populations, Arishem created the Eternals to counter them. With the reversal of the Blip,Earth has reached the necessary population for the birth of the Celestial Tiamut, which will result in Earth's destruction.