The first seat of the episcopal church itself, was started in 1535 upon the insistence of the Bishop of Santo Domingo, Don Sebastian Ramirez de Funleal, and was completed in 1544, at the time of bishop Juan López de Zárate. It was a basilica with three naves, and walls and pillars made of stone, each piece one by one. The monolithic columns of Mitla probably served as inspiration to the builders of the Catedral de la Virgen de la Asuncion, since this practice had disappeared in Europe centuries before. Its roof made of wooden beams was repaired between 1553 and 1581 due to the damage caused by earthquakes. The side chapels, where the famous retablista Andrés de la Concha worked between 1574 and 1594 also were damaged beyond repair by the earthquakes. Unfortunately there are no traces still remaining of his paintings.
Upon taking occupancy of the episcopal headquarters, Bishop Monterroso, proposed to the council that the naves be extended further back, and that the cover of the church be in a doom shape, which sparked a grand controversy. The works were completed around 1680. But the earthquakes of 1694 and 1714, two of the most serious in Oaxaca, severely damaged the building. After several years of reconstruction, during Christmas of 1730 the church was inaugurated, and 3 years later in 1733, it was consecrated by Bishop Santiago y Calderon.
There was little change until the second half of the 19th century. But in 1870 following further tremors, a remodeling process began that gained momentum starting in 1887, when Monsignor Eulogio Gillow took charge of the episcopal seat, who was later elevated to the rank of archbishop in 1891. Architecturally, the principle distribution of the Cathedral of Oaxaca is the basilica with three naves and the side chapels. Its cross shaped foundation dates back to the Roman architecture of the first Christian temples. However there was a different interpretation of the pattern mentioned, being that the cross is not in the last third of the longitudinal axis, perhaps due to the expansion of the church in the 17th century, in addition to lacking an apse. Another feature is the succession of three altars, the choir and the spaces for the parish, along the main nave. The Altar of Atonement, which precedes the main entrance of the temple, is associated with the popular spirit of the rites celebrated upon it. The same cannot be said for the stern choir and the wide presbytery where the main altar is located. The sequence ends at the back wall, where the Altar of the Kings once was, and now holds the piece of the Altar of the Holy Spirit.
The frequency of earthquakes in the region explains the cautious height of 16 meters (52 feet) in the main nave, the two meter sections on the composite Tuscan pilasters, and similarly the thickness of the walls and buttresses. Vaida vaults cover the main nave, the arms of the cross sections, and the side naves. On the lower level, barrel vaults extend over the side chapels, which provide a constructive advantage: the walls that divide act as powerful thrusts that support strong sides.
The look of the main entrance with squared proportions, richly represents the Baroque style. The divisions on the doors with diverse reliefs and niches with figures of saints between the columns, decorated columns, plinths, arches and completely saturated fringes, all contribute to increase the effect of visual vibration that is found on this entrance.