The first Spaniards arrived in the city on 15 November 1533. Francisco Pizarro officially arrived in Cusco on 23 March 1534, renaming it the "Very noble and great city of Cusco". The many buildings constructed after the Hispanic invasion have a mixture of Spanish influence with Inca indigenous architecture, including the Santa Clara and San Blas neighborhoods. The Spanish destroyed many Inca buildings, temples and palaces. They used the remaining walls as bases for the construction of a new city. Cusco stands on layers of cultures, with the old Tawantinsuyu built on Killke structures, and the Spanish having replaced indigenous temples with Catholic churches, and palaces with mansions for the invaders.
Cusco was the center for the Spanish colonization and spread of Christianity in the Andean world. It became very prosperous thanks to agriculture, cattle raising, and mining, as well as the trade with Spain. The Spanish colonists constructed many churches and convents, as well as a cathedral, university and Archbishopric. Just as the Inca built on top of Killke structures, Spanish buildings were based on the massive stone walls built by the Inca.
A major earthquake on 21 May 1950 caused severe localised damage in Cusco. The Dominican Priory and Church of Santo Domingo, which were built on top of the impressive Qoricancha (Temple of the Sun), were among the colonial era buildings affected. The city's Inca architecture, however, withstood the earthquake. Many of the old Inca walls were at first thought to have been lost after the earthquake, but the granite retaining walls of the Qoricancha were exposed, as well as those of other ancient structures throughout the city. Restoration work at the Santo Domingo complex was conducted in such a way as to expose the Inca masonry formerly obscured by the super structure without compromising the integrity of the colonial heritage. Cusco had also been the center of a major earthquake in 1650, and many of the buildings damaged in 1950 had been impacted by an earthquake only nine years previously.