Final answer:
The key factor in reducing indigenous populations was the introduction of European pathogens, especially smallpox, to which Native Americans had no immunity. Epidemic diseases had a catastrophic effect, being the primary cause of the population decline.
Step-by-step explanation:
The factor that greatly reduced the indigenous populations of the New World was primarily the introduction of European pathogens to which Native Americans had no immunity. Among these diseases, smallpox was responsible for the greatest number of deaths during the late fifteenth and early sixteenth centuries. Although factors like slavery and imperialism played roles in their decline, the lack of natural resistance and the introduction of diseases through European conquest and colonization proved to be the most devastating. Epidemic disease, particularly those spread through human contact and European domesticated animals, ravaged Indigenous communities, compounded by malnutrition and the breakdown of their social structures due to European incursions.