The Susquehannock, who had been decimated by smallpox and wars with the Iroquois, fled to Maryland and camped on Piscataway Creek near the fort occupied by the Piscataway Indians. The Susquehannock asked the governor to allow them to settle in Maryland because they had a treaty of peace and friendship with the colony. Worried about potential conflicts between the Susquehannock and the Piscataway, Maryland officials offered the Susquehannock land above the Potomac's Great Falls, a remote region that the Susquehannock found undesirable. In July 1675 trouble began. Murders and robberies in Virginia and Maryland were attributed by colonists to the Susquehannock, giving the incentive for 1000 troops, bolstered by native allies, to be raised against the Susquehannock.

Although the treaty with Maryland pledged eternal friendship with the Susquehannock, colonial forces murdered the Native leaders, who had come to parlay and deny any involvement in the murders, and laid siege to their encampment. With only 100 warriors, the Susquehannock managed to resist for six weeks, killing between 50 and 100 colonists. Eventually, the Susquehannock escaped and fled into Virginia, where they raided settlements at the heads of the Rappahannock and York Rivers in revenge, helping to trigger Bacon's Rebellion.