As commandant of the presidio of San Juan Bautista from its establishment in 1703 until his death, Diego Ramón played a key role in the development of Spanish Texas and the founding of missions in both Texas and Coahuila. Conjecturally, Querétaro has been given as his birthplace, but that is by no means certain. In the baptismal record of the parish of Santiago de Querétaro appears the name of a daughter, Juana, born to Diego Ramón and María de los Ríos. Record of the couple's marriage does not appear. There is reason to believe that Ramón had liaisons outside marriage that resulted in "natural" (i.e., illegitimate) children. His known offspring besides Juana included at least two other daughters and three sons: Domingofra24, Diego, and José. In 1716, while Don Diego remained at San Juan Bautista and Domingo led a new Texas entrada, José Ramón-whose name often is joined to Domingo's as though they were one person-was living at Boca de Leones (present Villadama, Nueva León). Living there also were his mother and two sisters.
In 1674 Diego Ramón was a soldier with Francisco de Elizondo's expedition to Fray Juan Larios's Coahuila mission (see BOSQUE-LARIOS EXPEDITION), "fourteen leagues" north of the Río de Sabinas. As a captain in 1687–88, Ramón was left in charge of Santiago de la Monclova during absences of Governor Alonso De León. His first entry into what is now Texas probably occurred in 1688, when he accompanied De León on the expedition to arrest the Frenchman Jean Jarry in the future Kinney County. After De León's death in 1691, Ramón served as governor ad interim of Coahuila. Following the ineffectual Texas expedition of Domingo Terán de los Ríos in 1691–92, he reported to the viceroy on the plight of the missionaries in eastern Texas. As a result, Gregorio de Salinas Varona, who had just been named Coahuila governor to succeed Ramón, undertook in the spring of 1693 an expedition to relieve the missionaries' distress. In 1699 Ramón led the founding expedition of Mission San Francisco Xavier, forty miles northwest of Monclova. On January 1, 1700, Ramón, now sargento mayor, officiated in the removal of San Juan Bautista Mission from the Río de Sabinas on the Coahuila-Nuevo León border to the site of present-day Guerrero, Coahuila, five miles from the Rio Grande. His association with this settlement, which ultimately included two other missions, endured until his death twenty-four years later. In March 1701, on recommendation of the bishop of Guadalajara, Captain Ramón was placed in command of a "flying company" charged with defending the Rio Grande missions. Two years later, the company was given permanent station in Presidio de San Juan Bautista, adjacent to San Juan Bautista Mission, with Ramón in command. In 1706, when smallpox swept through the native population, both in the mission settlement and in the montes, the captain and several of his soldiers accompanied a missionary priest into the Texas wilds to baptize dying Indians. The following year he led an expedition to the Nueces River to punish hostile Indians for raiding in Coahuila and Nuevo León, while exploring the country and recruiting Indians for the smallpox-ravaged missions (see RAMÓN EXPEDITION). In 1714 he received the French commercial agent Louis Juchereau de St. Denis, who had journeyed from Mobile seeking an entry to trade with the Spaniards, and sent him on to Mexico City for interrogation. In 1715, following an Indian uprising, Ramón crossed the Rio Grande with Fray Francisco Ruiz to return the rebellious natives to the missions.
Many of Ramón's descendants also were involved in historic events. In 1716 Manuela Sánchez Navarro (see ST. DENIS, MANUELA SÁNCHEZ NAVARRO DE), the granddaughter of Ramón's wife, Feliciana Camacho y Botello, was wed to St. Denis. She later joined her husband at the French post at Natchitoches, Louisiana. Also in 1716, Diego Ramón saw his son Domingo off for eastern Texas at the head of a new mission-founding expedition, accompanied by St. Denis as commissary and the younger Diego Ramón (Domingo's brother) as alferez. Domingo was to command the presidio of Nuestra Señora de los Dolores de los Tejas on the Neches River, then Nuestra Señora de Loreto de la Bahía Presidio at its first site. He officiated also in the founding of Nuestra Señora del Espíritu Santo Mission, near the presidio at La Bahía.
The second Diego Ramón, born in 1677, returned to Coahuila and ultimately came into possession of his father's hacienda, Santa Mónica. A third Diego Ramón, Domingo's son, succeeded to command of La Bahía upon his father's (Domingo's) death but was soon removed for negligence. He afterward became lieutenant of San Antonio de Béxar Presidio and temporarily commanded San Xavier de Horcasitas Presidio on the San Gabriel River. Assigned to serve as alferez at San Luis de las Amarillas Presidio (San Sabá), he was sent to Mexico City as a prisoner in 1757.
Diego Ramón the elder himself came under a cloud in his later years. In 1717, on the basis of complaints by Fray Antonio de San Buenaventura y Olivares, Governor Martín de Alarcón launched an investigation into the Ramón family's involvement in St. Denis's trade scheme. A royal decree dated January 30, 1719, ordered Don Diego's removal from San Juan Bautista Presidio and his reassignment to a distant post. The decree, not acted upon immediately, ultimately was nullified by Diego Ramón's death of natural causes.