Located on the upper floor, the Chapel of Aranzazú is the most prominent and visited space in the Regional Museum of San Luis Potosí. Dating to the second half of the 18th century, it is one of the finest examples of Potosino Baroque. It was built at the initiative of Fray Joaquín de Bocanegra, guardian of the former Franciscan convent, with construction beginning in 1749 and continuing until 1760.

The chapel is unique in that it was built on an upper level and features a covered atrium. It served as a private space, particularly for Franciscan novices. The finely carved stone façade features slender "estípites" (baroque pilasters) with shallow niches on either side. Above the doorway is a carved keystone bearing the coat of arms of Aranzazú, flanked by two Franciscan shields and a central medallion.

The mesquite-wood door is original and features high-relief carvings. Behind the altar and facing today’s Plaza de Aranzazú, there is a beautiful Baroque window—now one of the most iconic architectural features in the city of San Luis Potosí.