In this inquiry, students investigate one of the best-known stories in American history—the interaction between the Pilgrims and the Wampanoags that included the first Thanksgiving. The compelling question “Why did the Pilgrim–Wampanoag friendship go so wrong?” focuses on how the relationship between Native Americans and European settlers deteriorated over time. The Pilgrims’ initial contact with the Wampanoags in the winter of 1621 was not the first time Europeans and Native Americans met, but the interactions that followed have become a central part of the narrative of American history. As they complete this inquiry, students learn more about the history of colonial and Native American relations by responding to the compelling question with an argument about how the interactions between the Pilgrims and the Wampanoags changed over time.