Coyoacán was a city-state enemy to the Aztecs. These people welcomed Hernán Cortés and the Spanish, who used the area as a headquarters during the Spanish conquest of the Aztec Empire and made it the first capital of New Spain between 1521 and 1523. The village, later municipality, of Coyoacan remained completely independent of Mexico City through the colonial period into the 19th century.
Now it's the most culture-inclined part of the city, mostly due to the main campus of UNAM, the most important university in the country.
This is the center of Coyoacán: