After the sudden death of John Carter (Taylor Kitsch), a former American Civil War Confederate Army captain, Carter's nephew, Edgar Rice Burroughs (Daryl Sabara), attends the funeral. As per Carter's instructions, the body is put in a tomb that can be unlocked only from the inside. His attorney hands over Carter's personal journal for Burroughs to read, in the hope of finding clues explaining Carter's cause of death. Meanwhile, the mysterious Therns are secretly keeping watch on Burroughs' goal.
The anecdote recounts back to the Arizona Territory, where Union Colonel Powell (Bryan Cranston) arrests Carter. Powell, knowing about Carter's military background, seeks his help in fighting the Apache, insisting that Carter owes it to his country. Carter refuses, stating that he paid any debt he had when he lost his family. Carter escapes his holding cell, but is pursued by Powell and his cavalry. After a run-in with a band of Apaches, Carter and a wounded Powell are chased until they take to hiding in a cave that turns out to be the object of Carter's earlier searching, the "Spider Cave of Gold". A Thern appears in the cave at that moment; Carter kills him but accidentally activates the Thern's powerful medallion, and is unwittingly transported to a ruined and dying planet, Barsoom (Mars). Because of his different bone density and the planet's low gravity, Carter is able to jump high and perform feats of incredible strength. He is captured by the Green Martian clan, the Tharks and their Jeddak (chieftan) Tars Tarkas (Willem Dafoe). Tars instructs Sola (Samantha Morton) to watch over Carter which results in her feeding him a liquid that enables him to understand the Martian language.
Elsewhere on Barsoom, the Red Martian city of Helium led by Tardos Mors (Ciarán Hinds) and the mobile scavenger city of Zodanga led by Sab Than (Dominic West) have been at war for a thousand years. Sab Than is armed with a special weapon obtained from Matai Shang (Mark Strong), the leader of the Therns. He proposes cease-fire and an end to the war by marrying the Princess of Helium Dejah Thoris (Lynn Collins). Disguised as a soldier, the Princess escapes in a Helium ship.
When Tarkus wants John Carter to show off his jumping abilities, a Thark states the sightings of one ship from Helium and one ship from Zodanga scattering the Tharks to their hiding place. John Carter takes action and saves Dejah from falling. He does manage to kill some Zodanga soldiers and have a brief fight with Sab Than. Following the fight, which leads to Sab Than's ship retreating, John Carter is hailed as Dotar Sojat (which roughly translates to "My Right Arms") by Tars Tarkas due to his strength and skill. Tarkus even has Dejah given to him as part of the Thark spoils. Sometime after that, Carter, accompanied by Dejah, tries to find a way to get back to earth, and stumbles upon a temple ruin sacred to the Tharks where Sola encounters them and tries to stop them from entering, but fails. After discovering that an inscription stating a way back to Earth in the sacred river of Iss, Carter, Dejah, and Sola are caught by Sokoja (Polly Walker) and Tals Hajus (Thomas Haden Church). The three of them are sentenced to death due to the Thark code, but they are helped to escape by Tars Tarkas, who reveals to Carter that Sola is his daughter. When Tals and Sokoja find the prisoners gone, Tals states that Tarkus has "betrayed them." Carter, Dejah, Sola, and Woola (a Martian Calot - which is somewhat like a mixture of a lizard and a dog) embark on a quest to get to the end of a sacred river to find a way for Carter to get back home. They obtain information about the "ninth ray", a means of utilizing infinite energy and also the key to understanding how the medallion works. But they are later attacked by the Green Martian Clan of Warhoon, which were manipulated by Matai Shang to pursue them. After initially fleeing, Carter decides to buy the others time by fighting the horde himself as atonement for not being able to save his family.
Though defeating many Warhoon, Carter is ultimately overpowered and is saved when a Helium ship intervenes. Sab Than is also in the company of Tardos Mors as he mentions that Sab came alone and stated that he organized the rescue party. The demoralized Dejah grudgingly agrees to marry Sab Than as Carter is taken to Zodanga to be healed.
When Carter awakens, he is guided to Dejah's room. After the servant girls leave, Dejah gives Carter his medallion and tells him to go back to Earth. As Dejah leaves with Sab Than, Carter is captured by Shang in the form of a servant girl. In different Zodangan forms, Shang explains to Carter the purpose of Therns and how they manipulate the civilizations of different planets. Carter is able to make an escape thanks to Woola as he and Sola go back to the Tharks requesting their help. There, they discover Tarkas has been overthrown by Tal Hajus. Tarkas, Carter, and Sola are put on trial in a Colosseum battle with two enormous vicious creatures, the four-armed Great White-Apes. After defeating them and easily killing Hajus, Carter becomes the leader of the Tharks.
The Thark army charges on Helium and defeats the Zodangan army by killing Sab Than, while Shang escapes. Carter marries Dejah and becomes prince of Helium. On their first night, Carter decides to stay forever on Mars and throws away his medallion. Seizing this opportunity, Shang, in the form of a Helium Guard, sends him back to Earth. Carter embarks on a long quest, looking for clues of the Therns' presence on Earth and hoping to find one of their medallions; after several years he appears to die suddenly and asks for unusual funeral arrangements — consistent with his having found a medallion, since his return to Mars would leave his Earth body in a coma-like state. He makes Burroughs his protector, giving him clues about how to open the tomb.
The film reverts to the present, where Burroughs runs back to Carter's tomb and opens it, only to find it empty. A Thern, in the form of a man with a bowler hat, then appears, having followed Burroughs. But as he prepares to kill Burroughs, Carter appears and shoots the Thern, killing him. Carter then tells Burroughs that he never found a medallion. Instead, he devised a scheme to lure a Thern into revealing himself in order to get that Thern's medallion. After suggesting to Burroughs that he enjoy his life on earth and to try writing books (alluding to the fact that Burroughs is the real-life author of the "Barsoom" novels), Carter takes the Thern's medallion, whispers the code, and is then transported back to Barsoom.(En Wikipedia)
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