The ancient supercontinent of Pangaea breaks apart as the earth's tectonic forces cause the Americas to begin to drift away from Eurasia.
The first humans to reach the Western Hemisphere—the ancestors of modern Indian populations—migrate from Siberia into the Americas.
Inhabitants of Mexico successfully bioengineer maize—one of the world's most efficient sources of carbohydrates—from inedible teosinte grass.
Christopher Columbus sets sail from Spain, hoping to reach the East Indies by sailing due west across the Atlantic. Contrary to later mythology, Columbus is not the only European to recognize that the earth is round; he is merely the only European to underestimate the circumference of the planet by 10,000 miles, leading him to believe—erroneously—that a ship sailing west can reach China before its crew starves to death.
Christopher Columbus and his men unexpectedly land in the Bahamas, "discovering" the New World and initiating the Columbian Exchange.
Conquistador Hernán Cortés arrives at the Aztec capital of Tenochtitlan, leading a small army of several hundred Spanish soldiers. The Aztec leader, Moctezuma II, initially welcomes the Spanish into the city as honored guests.
Relations between the Aztecs and their Spanish guests turn sour, and Hernán Cortés somehow manages to imprison Aztec emperor Moctezuma within his own palace.
The Spanish occupiers of Tenochtitlan force the imprisoned Aztec emperor Moctezuma II to appear before his people, begging them to submit to Spanish rule. The Aztecs, furious at Moctezuma's betrayal, respond by stoning their leader to death and driving the Spanish out of the city.
Smallpox, introduced by an infected soldier in Cortés's army, spreads throughout Tenochtitlan, infecting as much as half the population in the Aztecs' magnificent capital city.
The Aztec emperor Cuahtémoc, with his people ravaged by smallpox and besieged by conquistadors, surrenders the capital city of Tenochtitlan to Spanish forces led by Hernán Cortés.
Smallpox strikes the Inca empire, killing more than 200,000 people, including the Incas' divine monarch Wayna Qhapaq, his chosen heir, and many of the empire's top military generals and civilian administrators. A smallpox-induced succession struggle devolves into civil war, which continues until the Spanish invade in 1532.
Spanish conquistador Francisco Pizarro, leading a force of only 168 men and 62 horses, captures Inca ruler Atawallpa and holds him for ransom.
Inca ruler Atawallpa fulfills his captor Francisco Pizarro's ransom demands, giving the Spaniard one room filled with gold and two rooms filled with silver. Rather than freeing Atawallpa as promised, Pizarro brutally murders him by garrote, plunging the Inca empire into disarray.
Francisco Pizarro captures the Incan capital of Cusco, finalizing Spanish conquest of the Inca empire.
Hernando De Soto's expedition of conquest into North America lands on the Gulf Coast of Florida. De Soto's party of 600 men, traveling with at least that many livestock, seeks to discover gold and an easy water passage through North America to China.
Hernando De Soto succumbs to disease somewhere in modern-day Arkansas. His soldiers bury his body in the Mississippi River, then flee to Mexico.
French explorer La Salle canoes the length of the Mississippi River, the first European to return to the region since the failed De Soto expedition 140 years before. Where De Soto found dense settlements surrounded with carefully tended fields of corn, La Salle finds an almost uninhabited wilderness overrun with buffalo.
On the southern Great Plains, the Comanche emerge as a distinct Indian nation, breaking away from the Shoshone to adopt a nomadic horseback lifestyle. The Comanche are the first North American Indian tribe to fully integrate the horse into their culture, and quickly use their equestrian skills to dominate the southern Plains.
Potato blight destroys the Irish potato crop, leading to the deaths of more than 1 million Irish by starvation and an exodus of perhaps 2 million emigrants from the country. The potato—originally cultivated in South America—has become the indispensable sustenance of the Irish people, and the crop's failure has catastrophic effects.