The pride of power of the Spanish preachers of religious art is reflected in the church of Santo Domingo built between 1541 and 1688. This work of heritage architecture, one of the first to be built in the colonized city, was affected by multiple earthquakes, interventions, and constructions that do not have a clear record. A total of 13 samples were taken from the lining mortar inside the cloister, central nave, and side chapel, following the nondestructive testing protocols and standards suggested by the research team. The analysis included mineral characterization studies and quantitative analysis by X-ray diffraction and scanning electron microscopy with microanalysis of the samples. The results showed the presence of volcanic aggregates and lime lining and joint mortars, mortars of rustic composition and coarse manufacture. The resolution of the data of mineralogical composition and texture has allowed us to corroborate the historical information described by the chroniclers and to date relatively the studied sites and to establish a hypothesis of constructive stages.