The central or major plot line of Mayflower by Nathaniel Philbrick is that of the relationship between the English settlers and the Wampanoag native people. He describes their tenuous working relationship as the settlers acclimate themselves to life in a harsh new land with the firmly established native peoples. Philbrick's writing explains how the unstable relationship between the two sets of people changes the landscape of the region forever.
In the beginning of the relationship, the Pilgrims relied on the Wampanoag people in order to survive their new living conditions, and the Wampanoag are able to assert their authority in the region. Massasoit benefits greatly from this early alliance. As more settlers arrive the situation and alliance begins to change, with conflict arising not only between the settlers and the native people, but also within the native people themselves.
This conflict ultimately leads to the Pequot War of 1637, which is one of the first examples of European genocide. At the heart of this and most of the conflicts is the need for land. Massasoit once again found a way to benefit from this need for land as he brokered land deals with the Englishmen. Philbrick goes on to write about the uneasy truce that Massasoit established and its ultimate demise as more Europeans arrived and the need for land outgrew the agreement.