About sixty miles from Provincetown Harbor lived Massasoit, an important Native American sachem, or leader. At one time, Massasoit had been the most powerful leader in the region, but disease had afflicted the Native Americans in the area and hit Massasoit’s people the hardest. From 1616 to 1619, it is estimated that what may have been the bubonic plague brought from Europe was responsible for killing close to ninety percent of the region's Native American population. Though the area in New England where the Pilgrims landed was sparse and unpopulated when they arrived, at one point it had been populated as densely as England.

Massasoit was the leader of the Pokanoket people. Before disease spread and killed many of the Pokanokets, there were around twelve thousand members of the tribe, including around three thousand warriors. After the plague, there were only a few hundred warriors left. Massasoit was under pressure from his neighbors to the west, the Narragansetts. Though his people struggled to survive and maintain their land, Massasoit found some support through an alliance he made with smaller groups. These groups all shared one common enemy, the Narragansetts, which still had around five thousand warriors.

Massasoit was engaged in this power struggle when the Pilgrims arrived.