A good illustration of how devastating epidemics in North America among the natives were is that when the first European explorers reached the coast on the west side of what is now the United States they found that part of the continent to be highly populated.
That was in the early 1500s. It was another couple hundred years before Europeans started colonizing and conquering those areas. By the time that started those populations were already reduced by around 90% from diseases that has spread across the continent from the Europeans on the east side.
Before those diseases wiped out so many natives no European colonists were able to survive in what is now the US and Canada without the approval and help of the natives. If the local natives didn't want a colony there, they removed it.
Yes, the colonists had guns and the natives then did not but the guns in those times weren't actually superior to bows and arrows. The guns might have better range, but their accuracy was much worse and they took longer to reload.
Before diseases that the colonists (unintentionally) brought greatly weakened the native tribes pretty much the only colonists that did OK were those that allied with a native tribe.
There were a bazillion tribes, and there was a lot of conflict between them including warfare. Some smaller tribes that were losing their wars with bigger tribes allied with some of the colonies to try to get help against the bigger tribes. Those were the colonies that were allowed the stay and thrive.
For a great look at what life was like in the New World before Europe became widely aware of it, and what happened afterwards the book "1491: New Revelations of the Americas Before Columbus" by Charles C Mann is quite good.