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Jesuit missionaries were the founders of the mining towns of San Antonio de Cuencamé and Mapimí. This religious order was also responsible for spreading the veneration of the Señor de Mapimí in these areas, which became one of the most important religious traditions in Nueva Vizcaya since the 18th century.
The town of Durango was founded on July 8, 1563, by the Basque captain Francisco de Ibarra. It became an important administrative center and the seat of government for the Kingdom of Nueva Vizcaya and the bishopric during the colonial period.

La Hacienda de San Diego de Navacoyán, located on the banks of the Tunal River in the present-day state of Durango, was another significant stop on the itinerary of the Camino Real de Tierra Adentro. Travelers needed to cross this river to continue their route towards Chihuahua and New Mexico.

The town of Nombre de Dios is considered the oldest settlement in Durango and is a significant point along the Royal Inland Road due to its contribution to the colonization process of northern Mexico.

The Chapel of San Antonio de Padua was built in the 18th century in the former hacienda of San Antonio de Juana Guerra, in the community of Amado Nervo, Nombre de Dios, Durango.

n the second half of the 16th century, the territory that currently comprises the state of San Luis Potosí was known as the "Gran Tunal," an extensive uninhabited area located between the present-day states of Querétaro, Saltillo, and Zacatecas.

The silver mines of San Demetrio were discovered in 1566, located 5 kilometers from the Real de Fresnillo. This discovery led to the surrounding area being populated with agricultural and livestock ranches, which later evolved into prosperous haciendas. By 1621, the site was officially named Real de San Demetrio de los Plateros.
After the initial explorations, the Spaniards found in the territory of present-day Zacatecas large expanses of open grasslands with high forage value, crucial for maintaining livestock herds.
Its location on the high part of the Sierra de Tlacotes, in the Cuisilique Valley, municipality of Ojocaliente, in the state of Zacatecas, makes Cueva de Ávalos a natural lookout point from which there is a panoramic view of the towns of Ojocaliente, El Refugio, and Palmillas, a region through which the Camino Real de Tierra Adentro extended.

The need to transport silver extracted from the mines of Zacatecas to the central part of the country, particularly to Mexico City, for smelting and minting influenced the emergence of the stretch of the Royal Inland Road between the city of Zacatecas and the town of Ojocaliente.