In 1600 the Wampanoag probably were as many as 12,000 with 40 villages divided roughly between 8,000 on the mainland and another 4,000 on the off-shore islands of Martha's Vineyard and Nantucket. The three epidemics which swept across New England and the Canadian Maritimes between 1614 and 1620 were especially devastating to the Wampanoag and neighboring Massachuset with mortality in many mainland villages (i.e. Patuxet) reaching 100%. When the Pilgrims landed in 1620, fewer than 2,000 mainland Wampanoag had survived. The island Wampanoag were protected somewhat by their relative isolation and still had 3,000. At least 10 mainland villages had been abandoned after the epidemics, because there was no one left. After English settlement of Massachusetts, epidemics continued to reduce the mainland Wampanoag until there were only 1,000 by 1675. Only 400 survived King Philip's War.

Still concentrated in Barnstable, Plymouth, and Bristol counties of southeastern Massachusetts, the Wampanoag have endured and grown slowly to their current membership of 3,000. The island communities of Wampanoag on Martha's Vineyard and Nantucket maintained a population near 700 until a fever in 1763 killed two-thirds of the Nantucket. It never recovered, and the last Nantucket died in 1855. The community Martha's Vineyard has sustained itself by adding native peoples from the mainland and intermarriage, but by 1807 only 40 were full-bloods. Massachusetts divided the tribal lands in 1842 and ended tribal status in 1870, but the Wampanoag reorganized as the Wampanoag Nation in 1928. There are currently five organized bands: Assonet, Gay Head, Herring Pond, Mashpee, and Namasket. All have petitioned for federal and state recognition, but only Gay Head (600 members but without a reservation) has been successful (1987). The Mashpee (2,200 members) were turned down by the federal courts in 1978.