The Spanish Empire began colonizing the Americas in 1492, when Christopher Columbus sailed from Europe to the Caribbean. The expansion of colonial control over the ensuring centuries led to almost the entirety of South America being turned into Spanish colonies, with the exception of Brazil (which was colonized by Portugal) and several smaller territories. As a result, the Spanish language spread across the continent and replaced the thousands of indigenous languages and dialects that were previously spoken. During this initial period of colonization, as many as 80% of the local population died or was killed. The spread of disease, enslavement, and brutal genocides committed by Spanish colonial forces greatly diminished the number of Indigenous people, enabling the Spanish’s takeover of the region . During the period of colonization, the eastern regions of the continent under control of the Spanish Empire were divided into several semi-autonomous provinces. These provinces included areas that resemble modern day Mexico, Guatemala, Venezuela, and Peru though their borders and areas of control changed over time.

Part of South American colonization was the introduction of Roman Catholicism through a long period of missionization. Between the 16th and the 19th centuries, many missions were sent from Europe to South America to evangelize in areas from Mexico to Argentina to Chile.