In 2148, the Earth's natural resources have been severely depleted. A starship named the Venture Star leaves Earth bound for a journey into deep space, with a crew of cryogenic men on board. 6 years later, in 2154, the RDA Corporation is mining a valuable mineral called unobtanium on Pandora, a lush, Earth-like habitable moon orbiting the gas giant Polyphemus located in the Alpha Centauri star system. Pandora, whose atmosphere is poisonous to humans, is inhabited by the Na'vi, 10-foot (3.0 m)-tall, blue-skinned, sapient humanoids who live in harmony with nature and worship a mother goddess called Eywa.
To learn about the Na'vi and Pandora's biosphere, scientists use Na'vi-human hybrid bodies called avatars that are operated via mental link by genetically matched humans. Jake Sully (Sam Worthington), a paraplegic former marine, replaces his twin brother, a scientist trained as an avatar operator who was murdered in a robbery. Dr. Grace Augustine (Sigourney Weaver), head of the Avatar Program, considers Sully an inadequate replacement and assigns him as a bodyguard. While protecting the avatars of Grace and scientist Norm Spellman (Joel David Moore) on their expedition to collect biological samples and data in the forest, Jake's avatar is attacked by a jungle predator thanator. Fleeing for his life, Jake strays from the rest of the group and gets lost in the forest. Neytiri (Zoe Saldana), a female Na'vi, stumbles upon Jake and reluctantly rescues him from Pandora's wildlife. Seeing portents from Eywa, she takes him to her clan's dwelling, Hometree; there, Jake meets Neytiri's father, clan chief Eytukan (Wes Studi). Neytiri's mother Mo'at (C. C. H. Pounder), the clan's spiritual leader, orders her daughter to teach the "warrior dreamwalker" their ways.
The head of Sec-Ops, the RDA's private security force, Colonel Miles Quaritch (Stephen Lang), promises Jake that the company will help him walk again if he gathers intelligence about the Na'vi. Hometree is on top of the richest deposits of unobtanium for hundreds of miles. When Grace learns that Jake is passing information to Quaritch, she relocates herself, Jake, and Norm to a remote outpost. Over three months, Jake grows close to Neytiri and her people. After Jake is initiated into the tribe, he and Neytiri choose each other as mates. Jake reveals his change of allegiance when he attempts to disable a bulldozer that threatens to destroy a sacred Na'vi site. When Quaritch shows a videofootage of Jake's attack on the bulldozer to Administrator Parker Selfridge (Giovanni Ribisi), the leader of the RDA colony, along with one of Jake's video diary entries, in which Jake admits that the Na'vi will never abandon Hometree, Selfridge orders Hometree destroyed.
Despite Grace's argument that destroying Hometree could affect the bio-botanical neural network to which Pandoran organisms are connected, Selfridge gives Jake and Grace one hour to convince the Na'vi to evacuate. When Jake reveals his original mission, Neytiri accuses him of betraying the entire tribe, and Jake and Grace's avatars are taken captive. Quaritch's forces destroy Hometree, killing Neytiri's father, as well as many others. Mo'at frees Jake and Grace, but they are unplugged from their avatars back at RDA headquarters and imprisoned. Trudy Chacón (Michelle Rodriguez), a pilot disgusted with Quaritch's brutal methods, breaks them out and flies them to the avatar link outpost. During the escape, Quaritch shoots and seriously wounds Grace.
The Na'vi are able to link mentally with some animals. To regain the Na'vi's trust, Jake takes a dangerous gamble and links with a Toruk, a powerful pterodactyl-like predator that has been tamed only five times in Na'vi history. Jake finds the refugees at the sacred Tree of Souls and pleads with Mo'at to heal Grace. The clan attempts to transfer Grace from her human body into her avatar with the aid of the Tree, but she succumbs to her injuries before the process can be completed.
Supported by the new Omaticaya chief, Tsu'tey (Laz Alonso), who acts as Jake's translator, Jake gives an inspiring speech to rally the Omaticaya clan and tells them to gather more Na'vi warriors in preparation for battle against the RDA. On the eve of battle, Jake prays to Eywa, via a neural connection to the Tree of Souls, to intercede on behalf of the Na'vi, although Neytiri warns him that Eywa does not take sides. Quaritch detects the mobilization of the Na'vi and convinces Selfridge to authorize a preemptive strike against the Tree of Souls, believing that its destruction will demoralize the natives.
At the same time, the Miner Train equip the majority of the team with new weaponry, and the Vikings even take a few weapons themselves. While Rodney and the robots leave to go get something.
The Na'vi fight back but suffer heavy casualties, including Tsu'tey and Trudy. Just when all seems lost, Pandoran wildlife unexpectedly join the attack and overwhelm the humans, which Neytiri interprets as Eywa answering Jake's prayer. Then the Robots arrive with the U.S.S. Missouri with giant copters and they fired the cannons at Quaritch's ship. Jake destroys a shuttle converted into a makeshift bomber before it can reach the Tree of Souls. Quaritch makes a narrow escape from his ship just as it is destroyed, and dons an AMP suit. But then Queen Chrysalis transforms into a huge, fire-breathing dragon! Quaritch stumbles upon and breaches the avatar link unit containing Jake's human body, exposing Jake to Pandora's poisonous atmosphere. Neytiri kills Quaritch and gets to Jake in time to save him. Then, Shining Armor stabs Queen Chrysalis in the heart as a result to her death. They reaffirm their love as she sees his human body for the first time.
With the exception of Jake, Norm, Max, and several other scientists, all humans are expelled from Pandora. Jake is seen wearing the insignia of the Omaticaya leader. The clan performs the ritual dedicated to Eywa that permanently transfers Jake from his human body into his avatar.
- Zecora, Stephen, Sharky, Mako, Willy, T.C., Hugs, Buzz, J.J., Socky, Skunky, 1206, The Miner Trains: (Steam Grindor, Steam Mech, Mucker, Steam Claw D., Steam Driller, Steam Sweeper, and Steam Exavator), Evan, Steamy, Puffy, Shai-Shay, Rattlesnake Jake, The Planet Trains: (Zip, Dazzlen, Dusten, Gustis, Rings, Uray, Tune, and Shiver), Dusty Crophopper, Bill and Ben, Rodney Copperbottom, Fender Pinwheeler, Wonderbot, Piper Pinwheeler, Crank Casey, Lug, Diesel, Hiccup, Toothless, Astrid, Stormfly, Snotlout, Hookfang, Fishlegs, Meatlug, Ruffnut and Tuffnut, Barf and Belch, Valka, Milo James Thatch, Kida Nedakh, Mole, Audrey Ramirez, Vinny Santorini, Joshua Sweet, Mrs. Packard, Cookie, Wilbur, Cardigan, Joy, Aranea, and Nellie guest star in this film.
- Ratchet, Commander Rourke, Helga Sinclair, and Queen Chrysalis will work for Quaritch in this film.
- Robots, How to Train Your Dragon 2, and Avatar were all made by 20th Century Fox.
- In the climax of the film, Queen Chrysalis transforms into a huge fire-breathing dragon
- Avatar and Thomas and Friends: Hero of the Rails were released on 2009
- The end credits for this film will be "My Heart Will Go On" dedicated to the composer of this film: James Horner.
- My Heart Will Go On (end credits)