In 1881, John Carter, a disillusioned Confederate veteran, searches for gold in the American West while to elude a detachment of Union soldiers. His quest for riches is interrupted when he takes refuge in a cave that turns out to be a portal. Carter is inadvertently transported to Barsoom, which he later learns is the planet Mars. The world is vastly different from Earth, characterized by warring alien races, exotic creatures, and advanced technology. Due to the planet's lower gravity and his Earth physiology, Carter discovers he has superhuman strength and the ability to leap incredible distances.

Amidst the chaos of Barsoom, Carter finds himself caught in the middle of a conflict between the cities of Helium and Zodanga, where he meets Princess Dejah Thoris of Helium. Dejah Thoris is desperate to save her people and is on the brink of marrying Sab Than, the conniving prince of Zodanga who wields a powerful weapon given by the mysterious Therns. The Tharks, a tribe of green-skinned nomads led by Tars Tarkas, capture Carter. He earns their respect through his unexpected fighting abilities and begins to form valued friendships within the tribe. As Carter adapts to his new environment, he becomes a pivotal figure in the destiny of Barsoom, fighting for the survival of its people.