The end of the Inca civilization and its final ruling authority came with the Spanish capture of the rebel Inca stronghold at Vilcabamba and the execution of the last of the Inca rulers, Tupac Amaru, in 1572. The conquest of the Inca Empire by the Spanish began 40 years earlier with the execution of the Inca's sovereign emperor, Atahualpa, by the conquistador Francisco Pizarro in 1532. The Spanish next set-up a puppet Inca government to help them control their newly acquired territory, but a rebellion began in 1536 and continued until the 1572 capture and sacking of Vilcabamba by the Spanish Viceroy of Peru, Francisco Toledo.
The Spanish conquest of the Inca Empire brought catastrophic long-term results to the indigenous people of the region. The indigenous population in the areas that were formerly part of the Inca Empire suffered a decrease traditionally estimated to be about 50 percent. Colonial rule brought with it exploitation, forced labor, cultural loss and forced relocations.
Most of the indigenous deaths occurred from the European infectious diseases that the Spanish conquistadors and colonists unknowingly brought with them. Lacking an acquired immunity to European diseases, such as measles and smallpox, the indigenous people suffered more fatalities as a result of the newly introduced illnesses than from the armed conflicts that followed the arrival of the conquistadors. A 1981 study suggested that by 1591, the collective waves of epidemics may have reduced the indigenous population in the Andes region by as much as 93 percent beginning from the time of the first contact with Europeans.