CGP Grey explains why so many indigenous Americans died when the colonists first came in the Americas. Most of the death work was done by the plagues. They didn’t had plagues like these before because you don’t have many animals in the Americas which could spread disease like you have in the Old Continent.
Also, in the Old Continent you could see very many cities, places where a big number of people would always flock, creating a great place for the plagues to evolve and kill over and over again. In the Americas the big cities were rare and thus, if any plague would come, then it will wipe a small village and then disappear.
A good video to watch as you learn that the effect of visiting a previously unknown place can lead to catastrophic consequences.