The novel is framed as an oral history dictated by an elderly man of the Mexica, the people of Tenochtitlan, to Spanish friars at the command of King Carlos V of Spain. Bishop Juan de Zumárraga of Mexico, serving as Apostolic Inquisitor and Protector of the Indians, has located the narrator, a former scribe, warrior, and merchant in his early sixties. He insists on being called Mexícatl rather than "Aztec" or "Indian." Interspersed throughout, Zumárraga's letters to the King express mounting revulsion at the narrator's candor, while the King orders the project's continuation, finding the chronicle more informative than the reports of Hernán Cortés, the Spanish conqueror of Mexico.
The narrator is born on the island of Xaltócan in the lake region surrounding Tenochtitlan in September 1466, given the childhood day-name Seven Flower. At age seven he receives his formal name, Chicóme-Xochitl Tliléctic-Mixtli, meaning Seven Flower Dark Cloud. His father, a master quarrier called Head Nodder for his great height, is overshadowed by Mixtli's domineering mother. His older sister Tzitzitlíni, called Tzitzi, is exceptionally beautiful, and his two closest friends are the aspiring painter Chimáli and the aspiring sculptor Tlatli. The island governor's son Pactli develops an obsessive interest in Tzitzi that looms over the family.
From about age seven, Mixtli's distance vision deteriorates steadily, earning him the mocking nickname Mole. Yet this handicap sharpens his close-range observation, and he teaches himself picture writing. A childhood visit to Tenochtitlan, during which he witnesses the dedication of the great Sun Stone, ignites his ambition. A mysterious, cacao-brown old man predicts that Mixtli's destiny is to look closely at the world and see it near and plain.
At roughly age twelve, Tzitzi initiates a sexual relationship with Mixtli by drugging him with a sacred mushroom. Their incestuous affair continues secretly for years while Pactli's pursuit of Tzitzi intensifies. Mixtli's friends receive invitations to advanced schools in Tenochtitlan, but Mixtli, lacking noble birth, is left behind. An invitation arrives from Nezahualpíli, the Revered Speaker (ruler) of Texcoco, to study at his court. There, Mixtli is assigned as companion to Nezahualpíli's new fifteen-year-old bride, Jadestone Doll, daughter of the Mexica ruler Ahuítzotl. The young queen proves sexually voracious and murderous, having her lovers killed and their skeletons preserved inside portrait statues. Mixtli engineers her exposure, leading to a spectacular trial. Jadestone Doll and the implicated Pactli are executed, but Mixtli is banished. Returning to Xaltócan, he learns that priests have discovered Tzitzi is no longer a virgin. She is delivered to the palace and disappears.
Mixtli volunteers for a military campaign against the rival city-state of Texcála, where he captures the legendary Armed Scorpion, a Jaguar Knight, or elite warrior, by severing the man's feet. The feat earns him rapid promotion. Using an unexpected inheritance of trade goods, Mixtli outfits a trading expedition southward with his young companion Cozcatl and Blood Glutton, a veteran warrior who had been his military instructor. In the Zapotéca city of Tecuantépec, he frees an indebted innkeeper named Gié Bele and her two daughters. Pursuing rumors of a rare purple dye along the coast, Mixtli and the younger daughter Zyanya barely escape the hostile Huave people who guard the source. During an earthquake they become lovers. Zyanya's name means "Always."
In the Chiapa country, the crystal artisan Master Xibalbá grinds Mixtli a topaz lens that corrects his lifelong nearsightedness. For the first time since childhood, he can see clearly at distance. Back in Tenochtitlan, the cacao-brown old man reveals a devastating truth: The inheritance Mixtli received was Tzitzi's bequest, earned when she sold herself to Ahuítzotl's menagerie of human curiosities. The disfigured person Mixtli once encountered in the menagerie and fled from in horror was his own sister, who later suffocated herself. Mixtli's father killed himself after learning the truth through the island governor Lord Red Heron's deathbed confession.
Ahuítzotl promotes Mixtli to the Eagle Knight order, an elite military rank, and sponsors a palace wedding for Mixtli and Zyanya. The feast is disrupted when Mixtli challenges his old enemy Chimáli. Young Cozcatl castrates and blinds Chimáli but lets him live. Ahuítzotl, furious at losing his palace artist, executes the blameless Blood Glutton as a substitute. Mixtli and Zyanya enjoy years of happiness in Tenochtitlan. Their daughter, called Cocóton, is formally named Ce-Malináli Zyanya-Nochípa. When Ahuítzotl constructs a new aqueduct despite warnings, the resulting flood devastates the city. Zyanya rushes out to save a drowning man and is swept away. Mixtli discovers the man was the blinded Chimáli. Zyanya's body is never recovered.
Consumed by grief, Mixtli wanders for over a year through western mountains and northern deserts. He locates Aztlan, the legendary homeland of the Aztéca, the ancestral people from whom the Mexica descend, on a marshy coastal island. An aged historian reveals that the Aztéca who departed were not heroic pioneers but outcasts expelled for adopting human sacrifice. Mixtli resolves that whatever their origins, the Mexica earned their greatness through achievement.
During the reign of Motecuzóma the Younger, accumulating omens trouble the empire: an eclipse, mysterious fires, comets, and reports of strange vessels offshore. Motecuzóma sends Mixtli to investigate Spanish castaways on the Maya coast, where Mixtli learns basic Spanish and determines the strangers are men, not gods. In the year One Reed (1519), Cortés lands with eleven ships. Mixtli travels with a diplomatic embassy, spying on the Spanish camp and encountering the interpreter Malintzin (also called Malinche or Doña Marina), a former slave the same age Mixtli's daughter would have been.
Despite Mixtli's recommendations to ambush the invaders, Motecuzóma refuses. Cortés defeats the Texcaltéca, hereditary enemies of the Mexica, and recruits them as allies. He massacres the population of Cholólan and marches into Tenochtitlan, where Motecuzóma becomes his hostage. When Cortés's lieutenant Pedro de Alvarado massacres unarmed Mexica celebrants during a festival, the war chief Cuitláhuac is appointed regent. Motecuzóma is brought before the enraged crowd and struck by a thrown stone; Mixtli kills him with an obsidian dagger. On June 30, 1520, the Mexica drive the Spaniards from the island, but a single infected African soldier from a rival Spanish expedition introduces smallpox, killing nearly half the population. The young lord Cuautémoc becomes the last Revered Speaker. Cortés besieges the island, reducing its defenders to starvation. When Cuautémoc attempts to escape by canoe, he is captured on August 13, 1521.
In the colonial aftermath, Mixtli serves as interpreter for Cortés, witnessing Cuautémoc's torture and execution on fabricated charges. He deserts and returns to Béu Ribé, Zyanya's elder sister, whom he married in a loveless arrangement after Zyanya's death. Béu confesses she has loved him since youth, and Mixtli realizes he squandered decades of potential love. In their final years, the couple subsists by selling embroidered Mexica eagle emblems. Spanish buyers insist the eagle hold a snake rather than the traditional ribbon symbol, and this invented detail becomes embedded in national mythology.
When the chronicle is complete, Bishop Zumárraga convenes an Inquisition tribunal. Mixtli refuses to recant, smiling when told he will not reach the Christian Heaven. He is burned at the stake, declaring that if selected for the Flowery Death, the honorable sacrificial death of his people, even on an alien altar, he would not degrade the dignity of his going. The King's letter granting Mixtli a comfortable house and pension arrives too late.