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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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Ferdinand Magellan's ships are the first to circumnavigate the globe. Magellan himself is killed by natives in the Pacific.
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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' men—nearly 800 in total—are killed as they try to escape Tenochtitlan after the death of Moctezuma.
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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 Native Americans in the New World in Valladolid, Spain.
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Santa Fe, the capital of present-day New Mexico, is founded.
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It takes 12 years of fighting for the Spanish to subdue the Pueblo Indians in New Mexico.
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Madrid rises against Napoleon's occupying troops, beginning the Spanish War of Independence. Spanish colonies in South America use the opportunity to start agitating for independence themselves.
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Mexico is founded with a Republican Constitution. Spanish rule in North America comes to an end.