How Did Smallpox Affect Indigenous Populations?

Smallpox was the most deadly of the Old World diseases imported to the Americas after 1492, and the one that played the largest role in the Spanish conquests of the Aztec and Inca empires. Caused by the variola virus, it killed roughly 30 percent of those it infected in populations with no prior exposure, and left many survivors blinded or disfigured. Among the indigenous peoples of the Americas, who had no inherited or acquired immunity, mortality rates were often far higher, reaching 80 or 90 percent in some communities. The recurrent epidemics of smallpox, together with the related epidemics of measles, influenza, and other Old World diseases, killed tens of millions of people and were the most important cause of the demographic collapse of the Indigenous Peoples of the Americas.

This page focuses on the specific role of smallpox — its biology, its transmission, the major epidemics in the Americas, and its impact on the indigenous populations and on the Spanish conquests.

The Nature of Smallpox

Smallpox is caused by the variola virus, which evolved from a related virus in African or Asian rodents and became established as a human disease thousands of years ago. The disease existed in two main forms: variola major, the more severe form, and variola minor, a milder form. Variola major was a brutal illness that killed roughly 30 percent of those infected. The infection began with fever, headache, and severe back pain; after a few days, a characteristic rash developed on the face and extremities, with raised pustules that eventually scabbed and fell off. Survivors were often left with permanent scarring and sometimes blindness. The disease spread through close contact with infected individuals, and the incubation period of about 12 days meant that infected individuals could travel considerable distances before showing symptoms, helping the disease spread rapidly.

Why Smallpox Was So Deadly in the Americas

The catastrophic impact of smallpox on indigenous Americans was a direct consequence of the long biological separation of the Eastern and Western Hemispheres. The peoples of the Old World had been exposed to smallpox for thousands of years, and repeated epidemics had selected for genetic variants that conferred partial resistance. Most Old World adults had survived childhood exposure and were immune for life. Indigenous Americans had no such history. The variola virus had evolved in the Old World, the indigenous peoples of the Americas had never been exposed to it, and they had no inherited or acquired immunity. When the disease arrived, it encountered a population of all ages equally vulnerable, and mortality was correspondingly high. Some researchers have suggested that higher mortality was also compounded by malnutrition, stress, and concurrent infections.

The First American Epidemics

The first major smallpox epidemic in the Americas struck Hispaniola in 1518 or 1519, possibly carried by Spanish colonists or enslaved Africans. It spread rapidly through the native Taíno population, which had already been reduced by enslavement and other diseases, and contributed to the near-extinction of the indigenous peoples of the Caribbean.

The 1520 Epidemic in Mexico

The most consequential single epidemic was the smallpox outbreak of 1520 in central Mexico. The disease arrived in April 1520 with the Pánfilo de Narváez expedition, sent from Cuba to arrest Hernán Cortés, who had defied the governor of Cuba by staying in Mexico. Among the members of the Narváez expedition was an enslaved African man infected with smallpox, and within weeks the disease had spread to the indigenous populations of the Veracruz coast.

The epidemic swept through the densely populated central plateau of Mexico, including the Aztec capital of Tenochtitlán. Tens of thousands of people died, including the emperor Cuitláhuac, who had succeeded Moctezuma in 1520. The disease also spread to surrounding regions, killing perhaps 25 to 40 percent of the population of central Mexico within a year. The historical sources describe the dead piled in the streets, the houses emptied, and entire towns depopulated. The Spanish soldier Bernal Díaz del Castillo, who was present during the siege of Tenochtitlán, described the Aztecs as being in such a state of affliction that they seemed to be figures of death.

The 1520 epidemic drove the fall of the Aztec Empire to Cortés in 1521. With the Aztec leadership decapitated and large numbers of warriors and laborers dead, the resistance to the Spanish was fatally weakened. The disease also affected the Spanish forces, killing roughly a quarter of Cortés’s men, but their much smaller numbers meant that the relative impact was less devastating.

The 1524–1527 Epidemic in the Andes

Smallpox reached the Inca Empire before the Spanish. The disease was carried overland from Central America or possibly by shipwrecked Spaniards sailing along the Pacific coast, and it struck the Inca heartland around 1524 or 1525. The emperor Huayna Capac is generally believed to have died a year or two after the epidemic took hold, around 1527, along with many members of his court. The epidemic triggered a civil war of succession between Huayna Capac’s sons Atahualpa and Huáscar, which left the empire fatally divided when Francisco Pizarro and his small Spanish force arrived in 1532. The capture and execution of Atahualpa, the Spanish conquest of Cuzco, and the eventual incorporation of the Inca Empire into the Spanish colonial system all took place against the backdrop of the demographic catastrophe caused by smallpox.

Recurrent Epidemics in the 16th and 19th Centuries

The first epidemics were only the beginning. Smallpox continued to strike the Americas throughout the 16th, 17th, 18th, and 19th centuries, often in waves that killed survivors of earlier epidemics and their children. In Mesoamerica, major epidemics occurred repeatedly; the 1576 cocoliztli epidemic in central Mexico, now thought to have been a viral hemorrhagic fever rather than smallpox, killed perhaps 50 percent of the remaining indigenous population. In North America, the 1616–1619 epidemic, possibly involving smallpox, killed perhaps 90 percent of the native population in coastal New England. The 1837–1838 epidemic struck the Mandan, Hidatsa, and other Plains peoples with devastating mortality, contributing to the weakening of indigenous resistance to American expansion.

The Demographic Impact

The cumulative demographic impact of smallpox and the related Old World diseases was staggering. Estimates of the pre-Columbian population of the Western Hemisphere range from 60 million to 100 million or more. By 1600, the indigenous population had been reduced to perhaps 5 to 10 million, a decline of 80 to 95 percent in the worst-affected regions. In central Mexico, the population may have fallen from 20 to 30 million in 1519 to 2 to 3 million by 1600. The political vacuum created by depopulation allowed European empires to establish themselves across the hemisphere, and the labor shortage caused by indigenous depopulation drove the expansion of the Atlantic slave trade.

Smallpox and the Spanish Conquests

The role of smallpox in the Spanish conquests has been debated for centuries. The Spanish themselves sometimes recognized the role of disease: one 16th-century official wrote that “it pleased Our Lord to give them [the Aztecs] no warning, and to send the smallpox among them like the angel that slew the firstborn of Egypt.” The fall of the Aztec Empire cannot be explained by disease alone — Cortés’s military advantages, political divisions among indigenous peoples, and the strategic brilliance of Spanish-led indigenous alliances were all essential. But the smallpox epidemic of 1520 created the conditions in which the conquest became possible. The same is true of the Inca Empire, where the smallpox epidemic of 1524–1527 killed the emperor and triggered the civil war that made Pizarro’s conquest possible.

The Long Shadow of Smallpox

The history of smallpox in the Americas did not end with the 16th century. The disease continued to strike indigenous populations into the 19th century and is a haunting presence in the cultural memory of many native peoples, who incorporated the experience of plague into their oral traditions, religious practices, and historical narratives. Smallpox was finally eradicated globally in 1980, after a vaccination campaign led by the World Health Organization. The last natural case of smallpox anywhere in the world was recorded in Somalia in 1977. But the long legacy of smallpox in the Americas — from the deaths of millions in the 16th century to the conquest of the great indigenous empires — is a central chapter in the history of the Columbian Exchange and the global impact of European exploration.