The tribes tried to fight the encroachment by the colonists . Major conflicts took place in the Indian massacre of 1622 and the Second Anglo-Powhatan war , both under the leadership of the late Chief Powhatan 's younger brother , Chief '' Opechancanough '' . By the mid-17th century , the Powhatan and allied tribes were in serious decline in population , due in large part to epidemics of newly introduced infectious diseases , such as smallpox and measles , to which they had no natural immunity . The European colonists had expanded territory so that they controlled virtually all the land east of the fall line on the James River . Fifty years earlier , this territory had been the empire of the mighty Powhatan Confederacy
Indian massacre of 1622
Indian massacre of 1622
History of Virginia