The exhibition room dedicated to the Camino Real de Tierra Adentro showcases eight modes of transportation from the 18th to the 20th centuries. Through these objects, visitors can observe how the discovery of silver mines in Zacatecas was a powerful motivator for the Spanish to venture into the northern regions of New Spain. The Camino Real de Tierra Adentro, which extended from Mexico City to Santa Fe, New Mexico in the United States, played a crucial role in this expansion. The College of Propaganda Fide was funded by influential miners such as Ignacio Rivera de Bernárdez and Francisco Xavier Aristorena y Lanz.

The Franciscans of the Apostolic College of Propaganda Fide of Guadalupe, Zacatecas, played a leading role in this effort. From there, numerous groups of friars set out to establish missions in northern Mexico and present-day southern United States along the Camino Real. During their long journeys, they conducted mass baptisms and preached the gospel to the local inhabitants. This work was not easy, and many times they faced failure and martyrdom; however, their determination led them to the farthest regions of the Viceroyalty, including Texas and New Mexico.