Humans

• Sam Worthington as Corporal Jake Sully. Sully, the film's protagonist, is a disabled former Marine who becomes part of the Avatar Program. His military background helps the Na'vi warriors relate to him. Cameron cast the Australian actor after a worldwide search for promising young actors, preferring relative unknowns to keep the budget down.^{[32][dead link]} Worthington, who was living in his car at the time,^[33] auditioned twice early in development,^[34] and he has signed on for possible sequels.^[35] Cameron felt that because Worthington had not done a major film, he would give the character "a quality that is really real". Cameron said he "has that quality of being a guy you'd want to have a beer with, and he ultimately becomes a leader who transforms the world".^[36]
• Sigourney Weaver as Dr. Grace Augustine. Augustine is an exobiologist and head of the Avatar Program. She mentors Sully and is an advocate of peaceful relations with the Na'vi, having set up a school to teach them English.^[37] Weaver dyed her hair red for the part.^[38]
• Michelle Rodriguez as Trudy Chacón. Chacón is a combat pilot assigned to support the Avatar Program who is sympathetic to the Na'vi. Cameron had wanted to work with Rodriguez since seeing her in Girlfight.^[39]
• Giovanni Ribisi as Parker Selfridge. Selfridge is the corporate administrator for the RDA mining operation and one of the film's primary antagonists.^[40] Despite being the human in charge of the mining project, he only reluctantly authorises the attacks on the Na'vi after being persuaded by Quaritch that it is necessary, and the attacks will be humane. When the attacks are broadcast to the base, Selfridge displays discomfort at the violence.
• Joel David Moore as Norm Spellman. Spellman is an anthropologist^[41] who studies plant and nature life as part of the Avatar Program. He arrives on Pandora at the same time as Sully and operates an avatar. Although he is expected to lead the diplomatic contact with the Na'vi, it turns out that Jake has the personality more calculated to win the natives' respect.
• Stephen Lang as Colonel Miles Quaritch. Quaritch is the head of the mining operation's security detail. Fiercely loyal to his military code, he has a profound disregard for Pandora's inhabitants and serves as the film's primary antagonist. Lang had unsuccessfully auditioned for a role in Cameron's Aliens (1986), but the director remembered Lang and sought him for Avatar.^[39] Michael Biehn, who was in Aliens, read the script and watched some of the 3D footage with Cameron,^[42] but was ultimately not cast in the role.
• Dileep Rao as Dr. Max Patel, a scientist who works in the Avatar Program.^[43]

Na'vi

• Zoe Saldana as Neytiri. Neytiri is the film's female Na'vi protagonist, princess of the Omaticaya, the Na'vi clan central to the story, who is attracted to Jake because of his bravery.^[44] The character, like all the Na'vi, was created using performance capture, and its visual aspect is entirely computer generated.^[45] Saldana has also signed on for potential sequels.^[46]
• C. C. H. Pounder as Mo'at. Mo'at is the Omaticaya's spiritual leader, Neytiri's mother, and consort to clan leader Eytucan.^[47]
• Laz Alonso as Tsu'tey. Tsu'tey is heir to the chieftainship of the tribe, and at the beginning of the film's story, he is betrothed to Neytiri.
• Wes Studi as Eytucan. Eytucan is the Omaticaya's clan leader, Neytiri's father and Mo'at's mate.