The 1150 Project

The Cahokia fall AD 1150-1350 really did a number on North America - the number being 30%. The population then ticked back up until Caboto, the Floridian conquistadors, and the fishermen brought their diseases.

That 30% drop echoes what was going on in South America. Mesoamerica in-between seems to have weathered it better.

One contrafactual: if Europeans had arrived a few centuries earlier and faced much larger Indigenous populations and well-organized tribal confederacies. I'll take this seriously. Genetic-drift is a thing. The population-crash was obviously not driven by any disease known to Europe - or they'd not have suffered those diseases later. (Tuberculosis?) The bottleneck might even have left most of the survivors more vulnerable/susceptible: the surviving scattered hunter-bands lose resistance to salmonella-type diseases from unclean urban water, also don't need to process alcohol.

The contrafactual's problem is that Mesoamerica and (postapocalyptic) Peru had exactly those "well-organised tribal confederacies", and the first thing they did when the Spaniard came was to politick amongst themselves to overthrow their own elite in which course they bowed to the Spaniard. How loyal were the locals to Cahokia?