In 1696, smallpox, called "A great Mortality", devastated the Pamlico and neighboring Algonquian communities and reduced their populations.

The English assigned a reservation on Bennetts Creek to the Chawanokes (Chowan) before 1700; they reduced its sized from 12 to 6 square miles (16 km2) by 1707; the Chowanoke sold off land in 1713.

With growing white presence in eastern Carolina, more products of European origin were introduced to the natives.

Other practices persisted through the nineteenth century, including the women making baskets of rushes and silk grass.

The Machapungas and other tribes of Pamlico Sound, however, changed their alliances: before 1700 they were still at war with the Tuscarora and Coree, but in 1711 they sided with them against the English colonists.

The Hatteras, Weapemeoc (Paspatank or Pasquotank, Poteskeet, Perquimans and Yeopim) peoples were at that time the most acculturated groups; they remained on the side of the English.

A small number of natives were baptized as Christians by Anglican ministers throughout the late seventeenth and the eighteenth centuries.

Besides hunting and agriculture, the coastal groups still relied much on fishing and shellfish gathering, drying the products for preservation on reed hurdles over an open fire or in the sun.

The Tuscarora War disturbed the economic balance of many of the Algonquian groups: the fields of the Machapunga and their allies were destroyed by English colonists.

Marriage restrictions that prohibited marrying first cousins made it difficult to find mates within rapidly shrinking communities.

There were some colonial reports that two of 50 families among the Machapungas practiced male circumcision, but this was not typical of the Native Americans.