An analysis of the long-term impacts of the Columbian Exchange on Indigenous North American populations would show that Indigenous cultures faced the threat of extinction.
The Columbian Exchange introduced new diseases, to which Indigenous peoples had no immunities, resulting in devastating population declines. Additionally, the exchange led to significant cultural disruptions, territorial losses, and pressures from European colonization. While some Indigenous groups did resist European invasion and some new trade dynamics developed, the overarching consequence of the Columbian Exchange was the severe and often catastrophic impact on Indigenous populations and cultures.