Between 1821 and 1880, the Santa Fe Trail was primarily a commercial highway connecting Missouri and Santa Fe, New Mexico. From 1821 until 1846, it was an international commercial highway used by Mexican and American traders. In 1846, the Mexican-American War began. The Army of the West followed the Santa Fe Trail to invade New Mexico. When the Treaty of Guadalupe ended the war in 1848, the Santa Fe Trail became a national road connecting the United States to the new southwest territories. Commercial freighting along the trail continued, including considerable military freight hauling to supply the southwestern forts. The trail was also used by stagecoach lines, thousands of gold seekers heading to the California and Colorado gold fields, adventurers, fur trappers, and emigrants. In 1880 the railroad reached Santa Fe and the trail faded into history.

El Camino Real de Tierra Adentro is recognized throughout the United States of America and Los Estados Unidos de Mexico as a timeless route of trade and cultural exchange and interaction among Spaniards and other Europeans, American Indians, Mexicans, and Americans, which shaped individual lives and communities and affected settlement and development in the greater Southwest. Recognition of this route as an international historic trail will commemorate a shared cultural heritage and contribute in a meaningful way to eliminating cultural barriers and enriching the lives of people along El Camino Real de Tierra Adentro.

Once, thriving American Indian trade communities of Tiwa and Tompiro speaking Puebloans inhabited this remote frontier area of central New Mexico. Early in the 17th-century Spanish Franciscans found the area ripe for their missionary efforts. However, by the late 1670s the entire Salinas District, as the Spanish had named it, was depopulated of both Indian and Spaniard. What remains today are austere yet beautiful reminders of this earliest contact between Pueblo Indians and Spanish Colonials: the ruins of four mission churches, at Quarai, Abó, and Gran Quivira and the partially excavated pueblo of Las Humanas or, as it is known today, Gran Quivira. Established in 1980 through the combination of two New Mexico State Monuments and the former Gran Quivira National Monument, the present Monument comprises a total of 1,100 acres.

Santa Fe emerged as the hub of the overland continental trade network linking Mexico and United States markets—a network that included not only the Old Spanish Trail, but also the Santa Fe Trail and El Camino Real de Tierra Adentro. After the United States took control of the Southwest in 1848 other routes to California emerged, and use of the Old Spanish Trail sharply declined. Because of its rich history and national significance, the Old Spanish Trail has been designated as a national historic trail.

Pecos preserves 12,000 years of history including the ancient pueblo of Pecos, two Spanish Colonial Missions, Santa Fe Trail sites, 20th century ranch history of Forked Lightning Ranch, and the site of the Civil War Battle of Glorieta Pass.