What was one significant challenge faced by European powers during the early colonization of the Americas regarding indigenous populations?

One significant challenge faced by European powers during the early colonization of the Americas was the resistance from indigenous populations. Many native groups were not willing to give up their land or way of life, leading to conflicts. For example, when the Spanish arrived in present-day Mexico, they encountered the Aztecs, who fought back against the invaders. This resistance made it difficult for Europeans to establish control and settlements. Additionally, the cultural differences and misunderstandings often led to further tensions and violence between the two groups.