Isidro Félix de Espinosa was born in Querétaro on November 26, 1679. His parents, Isidro de Espinosa and Gertrudis de Miraelrío Tovar, had married in 1676, and had nine children, six of whom lived to adulthood. On March 18, 1696, Isidro Félix de Espinosa entered the Franciscan missionary College of Santa Cruz de Querétaro as a novice, and on March 19, 1697, made his profession. He accepted holy orders on December 17, 1700, and was ordained a priest on February 26, 1703. It seems likely that Espinosa was assigned to San Juan Bautista Mission in late 1703 or shortly thereafter.
On April 5, 1709, Espinosa, accompanied by Father Antonio de San Buenaventura y Olivares, Capt. Pedro de Aguirre, and fourteen soldiers, left San Juan Bautista and marched to the site of future San Antonio. There the padres were much impressed by the availability of water and the prospects for Spanish settlement. The Espinosa-Olivares-Aguirre expedition probed beyond the San Antonio River to the Colorado, where it hoped to make contact with the Tejas Indians who were rumored to have moved there. After finding no Tejas but learning that those Indians were still ill-disposed toward the Spanish, the expedition returned to San Juan Bautista on April 28, 1709.
Espinosa soon returned to Querétaro and remained there until he was named president of the new missions to be established in Texas by his missionary college. In 1716 he accompanied the expedition of Domingo Ramón, which established three Queretaran missions in East Texas: Nuestro Padre San Francisco de los Tejas, Nuestra Señora de la Purísima Concepción, and San José de los Nazonis.
Espinosa's missionary activities in Texas included participation in two more expeditions, those of Martín de Alarcón (1718) and the Marqués de San Miguel de Aguayo (1721). His contributions as a chronicler of early Texas history are without peer. Dubbed "the Julius Caesar of the Faith in New Spain," because he worked by day and wrote all night, Espinosa left a remarkable body of literature. It includes a biography of his friend, Antonio Margil de Jesús, and his Crónica de los colegios de propaganda fide de la Nueva España, called "the most important contemporary account of the Franciscans in Texas"; the work was reprinted in 1964.
Espinosa was recalled from Texas in late 1721 to serve as guardian of his missionary college and never returned to the province. In 1733 he was named president of the future Hospicio de San Fernando in Mexico City. In late life he returned to the college of Santa Cruz in Querétaro, where he died on February 14, 1755.