In the mid-17th century, the Franciscans erected the church and the convent.

Throughout time, it has witnessed many historical events and undergone various restorations and modifications. Since 1683, it served as the headquarters of the College of Missionaries of Propaganda Fide, one of the most important colleges for evangelizers in America. One of its most prominent students was Fray Junípero Serra, an important evangelizer in the northern part of the country.

In the early 19th century, with the start of the independence movement, the convent became the prison of the corregidor of Querétaro, Don Miguel Domínguez, and a few years later, it was taken by Iturbide to control Querétaro from the hill. Maximilian also was temporarily imprisoned in the Convent of the Holy Cross, and some say that if you are in the sanctuary's cemetery at midnight, you might encounter the shadow of Maximilian.

It is a place full of stories and legends, and among them, the Tree of the Crosses stands out. It is located in the convent's orchard and is a strange tree that has thorns in the shape of a cross, and each cross has three smaller thorns that resemble the crucifixion nails. It does not produce flowers or fruits and only has tiny leaves. According to legend, the missionary Antonio de Margil de Jesús planted his staff in the garden, which eventually grew into this strange tree.

The facade is sober and features a large portico with a triangular pediment.

Inside, there is a stone-carved replica of the Holy Cross that appeared in the sky on July 25, 1531, as according to legend, this event led to the city's foundation. Beautiful pink quarry stone altarpieces, some in Baroque style and others in Neoclassical style, can also be observed.