The Fall of Tenochtitlan, the capital of the Aztec Empire, was a decisive event in the Spanish conquest of the empire. It occurred in 1521 following extensive manipulation of local factions and exploitation of pre-existing political divisions by Spanish conquistador Hernán Cortés. He was aided by indigenous allies, and his interpreter and companion La Malinche.

Although numerous battles were fought between the Aztec Empire and the Spanish-led coalition, which was composed mainly of Tlaxcaltec men, it was the siege of Tenochtitlan that directly led to the downfall of the Aztec civilization and marked the end of the first phase of the Spanish conquest of the Aztec Empire. The Aztec population was devastated at the time by high mortality due to a smallpox epidemic, which killed much of its leadership. Because smallpox had been endemic in Asia and Europe for centuries, the Spanish had developed an acquired immunity and were affected relatively little in the epidemic.

The conquest of the Aztec Empire was a critical stage in the Spanish colonization of the Americas. With this conquest, Spain gained substantial access to the Pacific Ocean. Through that, the Spanish Empire could finally achieve its original oceanic goal of reaching the Asian markets.