Oto-Mangue speakers have been among the earliest to form highly complex cultures of Mesoamerica: the archeological site of Monte Albán with remains dated as early as 1000 BCE is believed to have been in continuous use by Zapotecs.
Other Mesoamerican cultural centers which may have been wholly or partly Oto-Manguean include the late classical sites of Xochicalco, which may have been built by Matlatzincas, and Cholula, which may have been inhabited by Manguean peoples.