I'm not sure what the GP is referencing specifically (the colonization of the Americas took hundreds of years on two continents after all) but we've got enough archaeological evidence to know that many indigenous cultures were in decline by the time the Spaniards first visited, and many entered a second decline after first contact but before they were conquered or fully economically exploited.

For example I've been studying the Mississippi river cultures [1] which left behind lots of mound villages formed into chiefdoms and paramount chiefdoms. Those cultures suffered a decline around the mid-15th century likely due to environmental changes which we can see in the distribution of villages and mounds changing. We can also see how warfare evolved based on defenses and the distribution of arable land to houses (i.e. are they clustered villages for defense or spread around their fields for efficiency?) Historians then compare them to the accounts of the Narvaez and de Soto expeditions which provides a baseline for post-contact (mid 16th), where we can also see a large decline and social restructuring before the English and French came in to finish the job (the Spaniards more or less gave up on that area as economically uninteresting except for the occasional slave raid).

[1] https://en.wikipedia.org/wiki/Mississippian_shatter_zone