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How did smallpox affect the Aztec Empire during the Spanish conquest?

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Map showing principal sites of Meso-American civilization, with the Mayan zone of influence shaded in green across southeastern Mexico, Guatemala, Belize, and parts of Honduras and El Salvador. The map highlights major Mayan, Aztec, and other ancient sites, as well as the extent of the Aztec Empire in central Mexico, using color-coded symbols and labels for notable cities and archaeological locations. — Pre-Columbian civilizations Principal sites of Mesoamerican civilization.

During the Spanish conquest, smallpox acted as a devastating catalyst that significantly weakened the Aztec Empire and facilitated its collapse.12

Introduced to the region by the Spanish, the disease spread rapidly among the indigenous population, causing catastrophic mortality rates. Its impact on the Aztec capital, Tenochtitlán, was particularly severe: during a critical five-month period while Hernán Cortés was regrouping his forces, the outbreak killed approximately half of the city's inhabitants. Among those who perished from the disease was the emperor Cuitláhuac, which created a leadership vacuum during a time of existential crisis.32

By drastically reducing the population and impairing the Aztecs' ability to organize a sustained military defense, the epidemic crippled their capacity to resist the Spanish siege. This demographic collapse, combined with the Spanish use of superior weaponry and strategic alliances with rival indigenous tribes, ultimately enabled the fall of the empire and the establishment of New Spain.12