Tlatelolco was a pre-Columbian altepetl, or city-state, in the Valley of Mexico. Its inhabitants, known as the Tlatelolca, were part of the Mexica, a Nahuatl-speaking people who arrived in what is now central Mexico in the 13th century. The Mexica settled on an island in Lake Texcoco and founded the altepetl of Mexico-Tenochtitlan on the southern portion of the island. In 1337, a group of dissident Mexica broke away from the Tenochca leadership in Tenochtitlan and founded Mexico-Tlatelolco on the northern portion of the island. Tenochtitlan was closely tied with its sister city, which was largely dependent on the market of Tlatelolco, the most important site of commerce in the area.

The altepetl was the local, ethnically-based political entity, usually translated into English as "city-state," of pre-Columbian Nahuatl-speaking societies in the Americas. The altepetl was constituted of smaller units known as calpolli and was typically led by a single dynastic ruler known as a tlatoani, although examples of shared rule between up to five rulers are known. Each altepetl had its own jurisdiction, origin story, and served as the center of Indigenous identity. Residents referred to themselves by the name of their altepetl rather than, for instance, as "Mexicas." "Altepetl" was a polyvalent term rooting the social and political order in the creative powers of a sacred mountain that contained the ancestors, seeds and life-giving forces of the community. The word is a combination of the Nahuatl words ātl and tepētl. A characteristic Nahua mode was to imagine the totality of the people of a region or of the world as a collection of altepetl units and to speak of them on those terms. The concept is comparable to Maya cah and Mixtec ñuu. Altepeme formed a vast complex network which predated and outlasted larger empires, such as the Aztec and Tarascan state.