What effect did European settlement have on American Indians—the people who already lived on this vast continent?

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In the long term, the answer to this question is obvious. As a consequence of European settlement, Indian people found themselves dispossessed of their lands, decimated by disease, and in many cases stripped of many aspects of their culture. But it is easy to forget that English settlement began in North America in 1607, and that the process of settlement and interaction that spanned this long period was complex and often resistant to narratives of "winners" and "losers" in the short term. 

In most cases, Native Americans attempted to incorporate Europeans into preexisting commercial and diplomatic networks. The newcomers quickly found themselves enmeshed in complex alliance systems. For example, the Wampanoag and the Pilgrims became friendly precisely because both needed allies. As more and more settlers arrived, Indian people began to lose lands, and often bloody conflicts occurred, such as King Philip's War in Massachusetts, and the Powhatan Wars in Virginia. Still, even as late as the War of 1812, Native peoples allied themselves with Europeans out of self-interest (or self-preservation.) Culturally, Indian peoples adapted European goods and beliefs to their own needs, and many Indian groups, decimated by war and disease, joined with others out of a need for protection. Many of the major eastern tribes, including almost all of the Six Nations, the Creek, the Seminole, and the Catawba were in fact formed by many different peoples who adopted each other into kinship networks. 

The point is not to downplay the impact of European contact on Native Americans, which was unspeakably tragic and utterly disastrous. Rather, it is to emphasize that Indians were not passive victims. They responded to European settlement through a combination of strategies that reflected their own complex histories.