The early town leaders of Arequipa wanted their own monastery of nuns. Viceroy Francisco Toledo approved their request and granted the license to found a private monastery for the nuns of the Order of Saint Catherine of Siena. The city of Arequipa set aside four plots of land for the monastery. Before it was completed, a wealthy young Doña María de Guzmán, the widow of Diego Hernández de Mendoza, decided to retire from the world and became the first resident of the monastery.
In October, 1580, the city fathers named her the prioress and acknowledged her as the founder. With her fortune now belonging to the monastery, work continued and the monastery attracted a number of women as novices. Many of these women were criollas and daughters of curacas, Indian chieftains. Other women entered the monastery to live as lay persons apart from the world.
The monastery, added to over the centuries, displays a mix of architectural styles, from the Spanish Sevillian style of its founders to the later mestizo colonial styles.
Predominant among the styles is the Mudejar, adapted the Spanish from the Moors, but rarely found in South American colonial buildings.