Antonio de Espejo was born in Torre Milano, a suburb of Córdova, Spain. He went to Mexico in 1571 with Archbishop Moya y Contreras as an officer of the Inquisition and there became a cattleman. By 1580 he had several ranches in the districts of Querétaro and Celayo. After implication in the murder of one of his servants he was sentenced to pay a heavy fine, and to evade payment he fled to Nueva Vizcaya, where he met survivors of the Rodríguez-Sánchez expedition. After receiving permission to head and finance an expedition to assist Fray Bernardino Beltrán in searching for the friars, Espejo enlisted fourteen men as an escort and furnished 115 beasts of burden loaded with supplies.
The party left for New Mexico on November 10, 1582, and followed the Río Conchos to the Rio Grande, which Espejo named Río del Norte. They crossed the river and remained eight days in pueblos San Juan Evangelista and Santiago, near the site of present Presidio, before recrossing the Rio Grande. On the Mexican side they traveled to the pueblos of the Piro Indians, where they learned that the Franciscans Francisco López and Agustín Rodríguez had been killed by the Tiguex Indians. When they reached the Tiguex country on February 17, Beltrán proposed that the expedition return, but Espejo was determined to explore the area to the east. He reached the Pecos River about thirty miles southeast of Santa Fe and followed the river south to the site of present Pecos, Texas. From there the Jumano Indians guided him and his men along what is now Toyah Creek, through Balmorhea, and on up Limpia Canyon by the sites of present Fort Davis and Marfa and down Alamito Creek to the Rio Grande.
Espejo reached San Bartolomé on September 10, 1583. His discoveries probably did more to stimulate the settlement of New Mexico and the exploitation of its mineral resources than did those of any other of the early explorers. He started back to Spain to urge the settlement of New Mexico but became ill at Havana, Cuba, where he died in 1585.