During Ousamequin's time as Massasoit, illness swept through Indigenous nations in a cataclysm that came to be known as The Great Dying. Settlers took advantage to expand their landholdings. While peace had held for 54 years, in 1675 war broke out in New England. The so-called King Philip's War pitted a pan-Indigenous alliance against the united colonies and had the highest per-capita casualty rate of all wars in American history. Dozens of colonial settlements were burned, including Providence and Warwick. Throughout the war, Metacom’s home base remained Sowams, and it was here at Potumtuk that he was assassinated and beheaded in August of 1676. As a warning to other native peoples, settlers at Plymouth hoisted Metacom’s head on a pike on the outskirts of the town, where it stood for twenty-five years.

After the war, some of the Pokanoket were relocated to the Shetucket Reservation in eastern Connecticut (under the oversight of Rev. James Fitch), where they continued to have their own sachem and social structure led in part by Metacom's sister Mattasquae and the Pokanoket war captain Pawbewonckenuck. Another group of refugees, known as the “Anawan Captives,” fled to a rural area of Rehoboth (now Seekonk, MA), and settled there. Captured survivors, including Metacom’s wife Wootonekanuske and his son Metom, were sold into slavery in Bermuda, while others were sold as far away as the Azores and the Caribbean. Those who identified as Pokanoket did not reveal their identity due to a colonial law that authorized any Pokanoket over 14 years of age to be killed on sight. As with other Indigenous New Englanders after the war, the Pokanoket did what they could to survive.