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The Aztec Empire was conquered primarily by Spanish conquistadors led by Hernán Cortés in 1519-1521. Utilizing a combination of superior weaponry, strategic alliances with discontented indigenous groups, and the spread of diseases like smallpox, the Spanish were able to weaken and ultimately defeat the Aztecs. The capture of their emperor, Moctezuma II, and the subsequent siege of Tenochtitlán culminated in the fall of the empire. The conquest marked the beginning of Spanish colonization in Mexico.

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