The twin mesas in central Coleman County have always been a landmark. One of the earliest maps of Texas shows a mountain near the center of the state with the notation, "Santa Anna's Peaks." The mountain and later the town were named for the Comanche war chief Santanna, or Santa Anna.

Texas Rangers camped at the foot of the mountain long before the area was settled, and cattle drives from South Texas to the northern markets passed through the gap in the mountain along a military road. The first permanent settlers soon built homes near a fresh water spring at the foot of the mountain. One enterprising settler stocked a supply of goods for trail drivers and settlers, starting the first business at "The Gap" in the early 1870s. In 1879 a petition to open a post office was filed, and the name of Santa Anna was chosen.