Santiago Juxtlahuaca is a town and municipality in Oaxaca in southeastern Mexico.

It is one of the oldest towns in the Mixteca region of Oaxaca, dating back to the 12th century AD.

The first Spanish visitor was the Dominican friar Gonzalo Lucero, who passed through in the year 1536 on a journey of exploration.

Three years later the monk Benito Hernández persuaded the natives to move to a new location, founded on 13 September 1542.

Between 1600 and 1633 the town was moved to its current location in the north of the valley, with the first streets laid out in the Spanish style.