Death. We can't be sure how many natives died as a result of European arrival, but it was definitely more than 50%, and some estimates place it as high as 90%. Historians used to blame European brutality, which was definitely a factor, but the main culprit was disease. Smallpox is usually seen as the villain of this story, but it's more likely that a series of diseases in combination did the damage. Along with smallpox, Americans were killed by measles and mumps, typhus, chickenpox, none of which they had been previously exposed to. This astonishing decrease of population was definitely the worst effect of these diseases, both psychologically and demographically, but the secondary effects were almost as bad. For one thing, the deaths of Aztec and Incan rulers touched off wars, which in turn made it easier to spread disease, because, you know, the number one way to catch smallpox is via hand-to-hand combat.