At Tlaxcala Cortés pacified his wavering Indian allies and rebuilt his military force. The key to victory, he believed, was the lake and he set out to build a fleet of prefabricated boats. It was at this time that Cortés wrote his long second letter to the King of Spain, outlining his actions since his arrival in Mexico-Tenochtitlán. Meanwhile, the Aztecs thought the Spaniards were gone for good. They elected a new king, Cuautemoc, "The Fallen Eagle." He was in his mid-20s, the son of Montezuma's uncle, Ahuitzotl and was an experienced leader.

The Aztecs cleaned the temple courtyards and again celebrated their fiestas in the traditional way. But by the end of September, people started to die of a mysterious and alien illness that had horrifying symptoms of "racking coughs and painful burning sores." The pestilence, smallpox, spread soon crossed the causeways into Tenochtitlán. It lasted 70 days, until late November, and killed a vast number of people.

At the end of December 1520, Cortés' army moved toward Tenochtitlán; the boats followed later, transported in pieces overland by 8,000 native carriers. The early stage of the siege saw the surrender of towns all around the lake. It must have been plain that Tenochtitlán was doomed. The Aztec leadership was divided, and the annals of Tlatelolco note that the Mexicans were already fighting among themselves. Soon Still the Aztecs would not surrender, even when only the city on the island was left.