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Columbus arrives in the Bahamas. Europeans are in the Americas to stay. Columbus eventually makes four voyages to the New World, but dies dejected and forgotten in Valladolid, Spain in 1506.
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The Treaty of Tordesillas is signed, dividing newly discovered overseas lands between Portugal and Spain.
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The encomienda system begins, granting Indians to Spanish encomenderos as slaves. The Spaniards are tasked with protecting the natives and teaching them Christianity. The system is rife with abuses.
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Geographer Martin Waldseemüler is first to use the name "America" to refer to newly-discovered continents, after Italian merchant, explorer, and cartographer Amerigo Vespucci. Columbus loses out on lucrative naming rights.
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Juan Ponce de León discovers Florida.
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Vasco Nuñez de Balboa becomes the first European to gaze upon the Pacific Ocean after cutting his way across the Isthmus of Panama.
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Ferdinand Magellan's ships are the first to circumnavigate the globe. Magellan himself is killed by natives in the Pacific.
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Fall of Tenochtitlan: Hernán Cortés and approximately 100 Spaniards capture the capital of the Aztec Empire.
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Cortés and his men conquer the entire Aztec Empire in what will later become Mexico.
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La Noche Triste: The "Night of Tears" in which almost two thirds of Cortés's men (nearly 800 in total) are killed as they try to escape Tenochtitlan after the death of Moctezuma.
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The Spanish import the first African slaves to the territory that will later become the United States.
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Juan Diego, a Mexican peasant, has an apparition of the Virgin of Guadalupe. Before long, Nuestra Señora de Guadalupe becomes the patron saint of the New World.
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Francisco Pizarro invades the Incan Empire and begins the conquest of Peru.
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Silver is discovered at Potosí in Bolivia. Spain begins to reap huge financial rewards from its New World colonies.
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Bartolomé de Las Casas and Juan Ginés de Sepúlveda debate the rights of Indians in the New World in Valladolid, Spain.
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St. Augustine, the first permanent Spanish settlement in what will later become the United States, is founded in what is now Florida.