The first construction of the cathedral began in 1545 with the rubble brought from the destroyed settlement in the Almolonga Valley, which had been a second attempt to found a town in the region.

The main altar stood under a dome, supported by sixteen columns lined with carey and decorated with elaborately worked bronze medallions.

In 1743 the Cathedral of Santiago de Guatemala was elevated to Metropolitan, whose festivities were celebrated with great pomp in February 1745.

Knowing that the bishop was already arriving, the festivities were arranged for the solemn reception and the illustrious dean of the Mitra, the church council, many members of the clergy, the distinguished neighbors and the prelates of the religious came out in carts pulled by mules to receive the visitor.

[2] Arriving at the archbishop's palace, they were received by numerous clerics, schoolboys from the Tridentine College and Seminary of Nuestra Señora de la Asunción.

[2] The Santa Marta earthquake of 1773 caused serious damage to the structure of the cathedral, and two of its chapels were restored at the beginning of the 19th century.

[5] One witness recounted that the earthquake felt like a combination of a long series of vertical and horizontal movements that made the ground appear to move in waves and rise up to a foot above its normal level.

[5] There was US$300,000 in losses; The affected towns apart from Antigua Guatemala, Dueñas, Parramos and Patzicía, were Jocotenango, San Pedro Sacatepéquez and Amatitlán.

[6] In 1897, the writer Ariza Poitevín described the conditions in which the ruins of the cathedral were in this way: "there were numerous temples and ruined buildings through whose cracks came out thick roots of the trees that had grown as a result of the abandonment in which the structures were found; The Cathedral could be visited, but with difficulty since it was so neglected that the atmosphere was fetid and humid and night birds and bats abounded, giving the place a gloomy appearance".