The Valley of Toluca was known as Matlatzinco valley in ancient times and home to at least four linguistic groups: the Matlatzinca, Otomi, Mazahua, and Nahua peoples. In the Postclassic period, the valley was ruled by a large powerful capital city whose ruins are located today in the village of Calixtlahuaca, just north of the city of Toluca. In 1478 the Mexica emperor Axayacatl conquered the Toluca Valley. The capital was stripped of its dynasty and power and some lands were distributed to kings and nobles from the Valley of Mexico.
One of the rivals of Calixtlahuaca was Tollocan, a minor city-state before 1478. When Axayacatl destroyed Calixtlahuaca, he placed the imperial provincial capital in Tollocan. Calixtlahuaca and other towns in the Toluca Valley paid tribute to the Aztec Empire through Tollocan. After the Spanish conquest, the name Tollocan was changed to Toluca. Archaeologists have not yet located a major Postclassic settlement within the modern city. Either the pre-Hispanic city of Tollocan was destroyed and covered over by the expansion of Toluca, or else the remains of Tollocan could lie outside of the modern city. A small Postclassic site was discovered on the hill called Tolochi, which is in the north of the modern city, but the remains seem too insubstantial to have been a major provincial capital. The tree of "Las Manitas Rojas", which literally means "little red hands", was planted before the Spanish Conquest in what is now the monastery of Nuestra Señora del Carmen. This tree is significant because it shows that Toluca was important enough for the Aztecs to create a botanical garden.
In 1521, the Spanish conquered the Valley of Toluca. Leading the troops was Gonzalo de Sandoval, one of Cortes' many sergeants. Toluca’s first governor was Pedro Cortés Coyotzin. The valley of Toluca and what is now the city of Toluca were included in the concession made by King Carlos V of Spain to Hernán Cortés