After John Carter's arrival, a boat of Green Martians arrive on the River Iss and are ambushed by the previously unknown Plant Men. The lone survivor is his friend Tars Tarkas, the Jeddak of Thark, who has taken the pilgrimage to the Valley Dor to find Carter.
Carter and Tars Tarkas discover that the Therns, rulers of Valley Dor, a white-skinned race of self-proclaimed gods, have for eons deceived the Barsoomians of the outer world by disseminating the myth that the pilgrimage to the Valley Dor is a journey to paradise. Most arrivals are killed by the beasts of Valley, the survivors enslaved by Therns.
Carter and Tars Tarkas rescue Thuvia, a slave girl, and attempt to escape, capitalizing on the confusion caused by an attack by the Black Pirates of Barsoom upon the Therns. They are separated during the attack: Tars Tarkas and Thuvia hijack a Black Pirate flier, while Carter fights his way aboard another, killing all but one of the Pirates, and rescuing a captive Thern princess.
Carter, talking with the captured Pirate Xodar, discovers that the Black Pirates, called the "First Born", also think of themselves as gods, and prey upon the Therns as the Therns prey upon others. He also discovers that the captive Thern is Phaidor, daughter of the "Holy Hekkador" (high priest) of the Therns. When their flier is recaptured by the First Born, they are taken to their land, built around the underground sea of Omean, below the lost sea of Korus and the Valley Dor. Both are located at the South Pole of Barsoom.
Once there, Carter is taken before Issus, the goddess of Barsoom; an ancient, evil woman who has manipulated her own people and the rest of Barsoom into maintaining an hierarchy with the First Born on top. Issus dictates the policies of the Therns through secret communications with them. The Therns, thinking they are receiving divine communications, do not realize that they are duped by their enemies.
Issus takes Phaidor into her service as a handmaiden for one Martian year. Carter is imprisoned, with Xodar as his slave as punishment for being defeated by Carter. Thereafter Carter treats him with honor, and thus gains in him a friend. In prison, they meet a young Red Martian captive from Carter’s home country of Helium. Soon thereafter, Carter and the youth are taken to the monthly games of Issus.
In the games, the handmaidens of a year before are sacrificed, and their bodies will be eaten by Issus and her nobles. Carter leads a revolt of the prisoners, killing many of the First Born. Carter and the youth almost kill Issus before the First Born suppress the revolt. Carter and the youth escape via underground tunnels, and give themselves up to guards unacquainted with the revolt to be returned to their prison island. Upon hearing the story of the revolt, Xodar rejects the notion of Issus’ divinity.
Carter, Xodar and the youth hijack a flier and escape. Soon after, Carter discovers that the youth is his son, Carthoris. The flier is damaged and must be abandoned in unknown territory. They encounter Thuvia, who describes the capture of Tars Tarkas by the green warriors of Warhoon (a clan rival to his own). Carter goes alone to rescue Tars Tarkas, but is discovered. After a chase, Thuvia is sent on alone mounted while the men attempt a last stand against the Warhoons. They are rescued by the Heliumetic navy; but do not find Thuvia.
Commanding one of the warships is Carter’s friend Kantos Kan; but the fleet is commanded by Zat Arras, a Jed (chieftain) of the hostile client state of Zodanga, and Carter is suspected of returning from Valley Dor, which is punishable by death. Tardos Mors, the Jeddak of Helium, and Mors Kajak, the Jed of Hastor (the grandfather and father, respectively, of Dejah Thoris, and thus Carter’s in-laws) are absent from Helium, having led fleets in search of Carter. Later, Carter discovers that Dejah Thoris is missing, believed to have taken the pilgrimage to the Valley Dor to find him.
Upon returning to Helium, Carter is tried for heresy by the Zodangans; but the people of Helium do not tolerate this. To avoid civil war, Carter's judgment is deferred for a year. Sola, the daughter of Tars Tarkas, arrives, having escaped the First Born.
Carter realizes that Dejah Thoris will be selected as a handmaiden of Issus, and thus will have only a year to live; wherefore he and his comrades go to rescue her. They uncover evidence that Thern spies are monitoring them, and Carter is kidnapped by the Zodangans. Carter refuses Zat Arras’ offer of freedom in exchange for endorsing Zat Arras as Jeddak of Helium, and is imprisoned. After half a year in a dungeon, Carter wins his freedom through a ruse, and the mission to the land of the First Born is launched, with secretly raised troop levies, ships, and many troops lent by Tars Tarkas.