In the mid-22nd century, humanity is mining a precious mineral called unobtanium on Pandora, a lush and Earth-like moon of the gas giant Polyphemus in the Alpha Centauri star system. The planet's atmosphere is toxic to humans, necessitating the use of "avatars," genetically engineered human-Na'vi hybrids that are remotely controlled by mentally linked human operators. Jake Sully, a paralyzed former Marine, is recruited to join the Avatar Program after his twin brother's untimely death. Given the opportunity to walk again through his avatar, Jake accepts the mission to infiltrate and spy on the indigenous Na’vi in order to help the corporation force them to relocate and make way for the mining operations.

As Jake's avatar is embraced by the native Na'vi tribe, he begins to appreciate the rich and vibrant culture of this alien society and the deep spiritual connection they share with their environment—particularly the sacred Tree of Souls. The Na’vi are led by the wise and stern Eytukan, the chief of the tribe, and his daughter Neytiri, a skilled and fierce warrior, takes on the task to teach Jake their ways. During his immersive training in their world, Jake grows increasingly sympathetic to the Na’vi's plight, finding himself emotionally and ethically torn between the military-industrial interests he was sent to assist and the alien culture that has accepted him as their own.