Tishomingo was named after the Chickasaw chief who died of smallpox on the Trail of Tears near Little Rock, Arkansas, after the Chickasaws had been removed from their original homelands in and around Tishomingo, Mississippi.

Before the founding of Tishomingo in 1852, the area was known as "Good Springs", for the presence of several springs that made the area a suitable campsite along the road between Fort Washita and Fort Arbuckle. A small town had replaced the old campsites with permanent structures and had been renamed "Tishomingo" by 1856 when it was designated as the Chickasaw capital. A post office was established in 1857.