At the time of European settlement in the area of Laredo, the predominant Native American tribe was the Coahuiltecans. The Coahuiltecans were not one unified people. Instead, they were various bands of nomadic hunter-gatherers who had shared linguistic and cultural traits. The Spanish recorded that they usually lived in bands of a few dozen people but at times had larger gatherings of between 100 and 500 members.

The Coahuiltecans moved with the seasons. As was typical of Native American nomads, they had very few possessions. In their camps, they built and lived in circular huts composed of woven mats draped over wooden poles. The Coahuiltecans who lived along the Rio Grande were somewhat more sedentary. The reliable resources that the river provided allowed these Coahuiltecans to build more substantial homes and move around much less. They used simple stone and wooden tools. They also were known to be proficient with the use of bows and arrows.

While they ate meat, such as venison and lizards, when they could get it, Coahuiltecans subsisted on a mostly vegetarian diet. This includes seeds, cactus fruit, and roots. Even deer dung was a food source for the Coahuiltecans. Spider eggs were a particular treat. A major staple of their diet was pecans. These were collected in the autumn and stored for consumption throughout the year. Mesquite beans were ground into a flour that could be eaten immediately or stored for some time.

Little information exists concerning the religion of the Coahuiltecans. We know that they would sometimes gather in larger numbers to dance through the night while undergoing a peyote-induced trance. Rock art and oral history describe a creation story in which the Universe is born from the Sun after a journey through the underworld where it meets the Moon. They also used the stars to chart the passage of time.