The name comes from Nahuatl and roughly translates to "in the River of the Dry Corn plants"[1] The area was settled by the Matlatzincas who were conquered by the Aztecs, making the area a border zone between the Aztec Empire and Purépecha lands.

Evangelization was carried out by Franciscans, who were followed by Spanish families bringing sugar cane and fruit trees to plant.

It was very important to the development of the area because of the irrigation system it constructed on its lands, which constituted much of what is now the municipality.

After arriving in the late 19th century, and receiving a warm welcome, General Juan N. Mirafuentes started a movement to make the village a municipal seat separate from Otzoloapan.

This was accomplished on April 5, 1879 with C. Juan de Dios Villafaña Salinas as the first municipal president.

[1] As a municipal seat in the State of Mexico, Zacazonapan was remodeled by Carlos Hank González in 1974.