The main cause of the fall of the Aztec Empire was the combination of internal strife and external pressures, particularly the arrival of Spanish conquistadors led by Hernán Cortés in 1519. The Aztec Empire faced challenges, including dissatisfaction among conquered peoples and political divisions that weakened its unity. Cortés exploited these internal factions, forming alliances with indigenous tribes who opposed Aztec rule. The introduction of European diseases, such as smallpox, devastated the native population, further weakening the empire. Ultimately, the combination of military conquest, disease, and alliance-building led to the rapid collapse of this once-powerful civilization by 1521.