Final answer:
Hernán Cortés was the Spanish conquistador who led the expedition that overthrew the Aztec Empire and established Spanish rule in Mexico.
Step-by-step explanation:
The Spanish conquistador responsible for leading the expedition that resulted in the fall of the Aztec Empire and the colonization of Mexico in the early 16th century was Hernán Cortés.
This noteworthy figure embarked on his voyage from the coast at Veracruz and reached the Aztec capital of Tenochtitlán, encountering a sophisticated civilization with elaborate infrastructure and profound religious practices, including human sacrifice.
Despite initial awe, Cortés facilitated the disintegration of the Aztec society primarily through strategic alliances with local tribes such as the Tlaxcalans, the introduction of European diseases like smallpox, and military confrontations. Ultimately, the capital, Tenochtitlán, fell after a three-month siege, leading to the establishment of Mexico City atop its ruins and cementing Spain's colonial expansion in the New World.