The Aguayo expedition, a project of the Marqués de Aguayo, resulted from the French invasion of 1719, which caused the Spanish to retreat from East Texas. In response to Aguayo's offer, the viceroy commissioned him to reoccupy the area. Aguayo gathered together a force of about 500 men, organized as a mounted infantry, which he called the Battalion of San Miguel de Aragón. Four thousand horses and other livestock provided transportation and provisions. Juan Rodríguez actedas guide.

After numerous delays the expedition crossed the Rio Grande, on March 20, 1721, and reached San Antonio on April 4. A detachment under Domingo Ramón occupied La Bahía del Espíritu Santo on the same day Aguayo reached San Antonio. Accompanied by the friars who had been in San Antonio since the French invasion, the main body of the expedition went on to East Texas. The party proceeded by way of the sites of present New Braunfels and San Marcos to a crossing of the Colorado River a few miles below the site of present Austin, crossed Little River at the Griffin Crossing east of the site of Belton and the Brazos near the site of Waco, marched southeast to the Old San Antonio Road above the site of Navasota and followed the road to the former Spanish settlements between the Trinity and Red River. Detours necessitated by heavy rains caused the Aguayo trail to skirt the Apache country and run in sight of the Balcones Escarpment.

The Indians east of the Trinity welcomed the Spanish, as did Louis Juchereau de St. Denis, who, as commander of the French forces in the area, agreed to withdraw to Natchitoches. While in East Texas Aguayo reestablished six missions: San Francisco de los Tejas (renamed San Francisco de los Neches), San José de los Nazonis, Nuestra Señora de la Purísima Concepción de los Hainai, Nuestra Señora de Guadalupe de los Nacogdoches, Nuestra Señora de los Dolores de los Ais, and San Miguel de Linares de los Adaes. He also reestablished the presidio of Nuestra Señora de los Dolores de los Tejas and built and garrisoned the presidio of Nuestra Señora del Pilar de los Adaes for the protection of the missions against hostile Indians or possible French encroachment.

In the fall of 1721 the members of the expedition not stationed in East Texas returned to San Antonio, which Aguayo strengthened by the establishment of a third mission there, San Francisco Xavier de Náxara, and by the rebuilding of San Antonio de Béxar Presidio. On a side trip to La Bahía he established the presidio of Nuestra Señora de Loreto and the mission of Nuestra Señora del Espíritu Santo de Zúñiga. He also initiated a direct sea route from La Bahía to Veracruz as a course of supply for the Texas mission establishments.

Leaving 219 of his men at various presidios in Texas, Aguayo returned to Coahuila, where the force was disbanded on May 31, 1722. The expedition resulted in the increase in the number of missions in Texas from two to ten, the increase in the number of presidios from one to four, the strengthening of the military force from fifty to 269 soldiers, and the establishment of so definite a Spanish claim to Texas that it was never again disputed by France or by the French in Louisiana. See also SPANISH TEXAS, SPANISH MISSIONS.