Documented smallpox epidemics in the New World [31]YearLocationDescription
| 1520–1527 | Mexico, Central America, South America | Smallpox kills millions of native inhabitants of Mexico. Unintentionally introduced at Veracruz with the arrival of Panfilo de Narvaez on April 23, 1520 [32] and was credited with the victory of Cortes over the Aztec empire at Tenochtitlan (present-day Mexico City) in 1521. Kills the Inca ruler, Huayna Capac, and 200,000 others and weakens the Incan Empire. |
| 1561–1562 | Chile | No precise numbers on deaths exist in contemporary records but it is estimated that natives lost 20 to 25 percent of their population. According to Alonso de Góngora Marmolejo, so many Indian laborers died that the Spanish gold mines had to shut down. [33] |
| 1588–1591 | Central Chile | A combined smallpox, measles and typhus plague strikes Central Chile contributing to a decline of indigenous populations. [34] |
| 1617–1619 | North America northern east coast | Killed 90% of the Massachusetts Bay Indians |
| 1655 | Chillán, Central Chile | An outbreak of smallpox occurred among refugees from Chillán as the city was evacuated amidst the Mapuche uprising of 1655. Spanish authorities put this group in effective quarantine decreeing death sentences for anyone crossing Maule River north. [35] |
| 1674 | Cherokee Tribe | Death count unknown. Population in 1674 about 50,000. After 1729, 1738, and 1753 smallpox epidemics their population was only 25,000 when they were forced to Oklahoma on the Trail Of Tears. |
| 1692 | Boston, MA | |
| 1702–1703 | St. Lawrence Valley, NY | |
| 1721 | Boston, MA | |
| 1736 | Pennsylvania | |
| 1738 | South Carolina | |
| 1770s | West Coast of North America | Kills over 30% of indigenous peoples on the West Coast of North America |
| 1781–1783 | Great Lakes | |
| 1830s | Alaska | Reduced Dena'ina Athabaskan population in Cook Inlet region of southcentral Alaska by half. [36] Smallpox also devastated Yup'ik Eskimo populations in western Alaska. |
| 1860–1861 | Pennsylvania | |
| 1862 | British Columbia, Washington state & Russian America | Known as the Great Smallpox of 1862, an outbreak of smallpox in a large encampment of all indigenous peoples from around the colony on June 10, 1862, dispersed by order of the government to return to their homes, resulted in the deaths of 50-90% of the indigenous peoples in the region [37] [38] [39] [40] [41] |
| 1865–1873 | Philadelphia, PA, New York, Boston, MA and New Orleans, LA | Same period of time, in Washington D.C., Baltimore, MD, Memphis, TN, Cholera and a series of recurring epidemics of Typhus, Scarlet Fever and Yellow Fever |
| 1869 | Araucanía, southern Chile | A smallpox epidemic breaks out among native Mapuches, just some months after a destructive Chilean military campaign in Araucanía. [42] |
| 1877 | Los Angeles, CA | |
| 1902 | Boston, Massachusetts | Of the 1,596 cases reported in this epidemic, 270 died. |