The Texas A&M University-San Antonio Campus was built on land that once was conveyed by Spanish and Mexican land grants and traversed by several branches of El Camino Real de Tierra Afuera del Oriente (also known as El Camino Real de los Tejas National Historic Trail). The first inhabitants of the area were Native Americans, who, at the time of discovery by Spanish explorers, were Coahuiltecans. The earliest grant for this site was made to Mission San José y San Miguel de Aguayo in 1720, followed by a grant made to Mission San Francisco de la Espada, founded in 1731 following its transfer from east Texas. Eventually, interspersed within these mission lands were many private Spanish and Mexican land grants made to soldiers and citizens of Béxar. Vaqueros drove thousands of cattle from the mission and private ranch herds eastward to Louisiana in support of the American Revolution and Bernardo de Gálvez's battles against the British along the Gulf of Mexico and Mississippi River.
In 1808, Juan Ignacio Perez (1761-1830) received a large five-league Spanish land grant on both sides of the Medina River. In 1781, he married Clemencia Hernandez and became involved with ranching. He purchased the Old Comandancia, later known as the Spanish Governor's Palace, from the Menchaca family. Along with his military and political success following the Battle of Medina (1813) on these lands, he was also a leading cattleman of the region. Smaller Mexican grants were eventually made to Jose de los Angeles (Angel) Navarro (1784-1836), brother of Jose Antonio Navarro, alcalde of San Antonio de Bexar and land commissioner, and Jose Antonio de la Garza (b. 1776), one of the largest landowners in San Antonio. A large portion of campus is situated on the Spanish land grant to Fernando Rodriguez, son-in-law of Juan Ignacio Perez.