The massacre of the nobles prompted a citywide uprising against the hated Spanish, who were forced to flee Tenochtitlán on June 30, 1520, across a causeway in Lake Texcoco amid ferocious fighting. Some 600 Spaniards and several thousand of their Tlaxcala allies perished in the escape, many of them laden with gold they had collected in Tenochtitlán. For the Spaniards it was La Noche Triste (the night of sorrow), while for the Aztecs it was no doubt a fitting revenge and a great triumph. Visual Source 13.4, from a Tlaxcala codex, depicts the scene. Cortés and his Tlaxcala allies to the left of the image are shown on the causeway, while many others are drowning in the lake, pursued by Aztec warriors in canoes.

While the Aztecs may well have thought themselves permanently rid of the Spanish, La Noche Triste offered only a temporary respite from the European invaders. Cortés and his now diminished forces found refuge among their Tlaxcala allies, where they regrouped and planned for yet another assault on Tenochtitlán. Meanwhile, smallpox had begun to ravage the Aztec population, which lacked any immunity to this Old World disease. The Florentine Codex described the situation: “An epidemic broke out, a sickness of pustules. . . . [The disease] brought great desolation; a great many died of it. They could no longer walk about . . . no longer able to move or stir. . . . Starvation reigned, and no one took care of others any longer. . . . And when things were in this state, the Spaniards came.”

In mid-1521, Cortés returned, strengthened with yet more Mesoamerican allies, and laid siege to the Aztec capital. Bitter fighting ensued, often in the form of house-to-house combat, ending with the surrender of the last Aztec emperor on August 13, 1521. In Tenochtitlán, all was sorrow and lamentation, as reflected in some of the poetry of the time: