In the early 1600s, European explorers and fishermen brought new diseases across the ocean. For Indigenous people, who had no immunity to them, the germs were deadly. From 1616 to 1619, an epidemic swept the coast from Maine to Narragansett Bay, devastating Native nations in its path. The Wampanoag people lost at least 75% and as much as 90% of their entire population.

The village of Patuxet, later known as Plymouth, was home to about 2000 people. When the disease arrived, nearly all of the people of Patuxet died. Only one survivor is known by name: Tisquantum.

Despite the horrific impact of the epidemic, regional Indigenous communities were not wiped out. They survived and continued.

The disruptions of the Great Dying created new circumstances for the Wampanoag.

On the other side of Narragansett Bay, the Narragansett nation largely escaped the disease. With the Wampanoag in crisis, Narragansett leaders pressured the Wampanoag sachem Ousamequin to pay them tribute. This would have afforded Wampanoag communities protection by the Narragansett but aligning with a powerful neighbor also had risks.

In the face of many uncertainties, Ousamequin and his council formed an alliance with the English colony at New Plymouth.