Seneca, the western-most member of the Haudenosaunee Confederacy, played a major role in the dispersal of the Huron-Wendat, Petun and Chonnonton in the mid-17th century. Much of southern Ontario then became Seneca hunting territory, until Ojibwa expansion into this region confined Seneca influence to south of the Great Lakes. Periodically at war with New France, all Seneca villages were burned by Governor Denonville in 1687. Revenge was extracted through the destruction of Lachine, outside Montréal, two years later (see Lachine Raid). After construction of the French fort at Niagara in the 1720s, the western Seneca frequently sided with the French in conflicts with the English. These same western Seneca in 1763 joined Obwandiyag and his followers against the English, who had taken possession of former French posts in the Great Lakes.

During the American Revolution, the full Seneca supported the royal cause, but only a small segment chose to follow Joseph Brant after the war to the Six Nations Reserve in Canada. Most of the Seneca negotiated peace with the Americans, and still reside on reservations in the US guaranteed at that time. In 1799 the Seneca Chief, Handsome Lake, experienced a vision which still influences the practice of traditional Iroquois religion in both Canada and the US.

See also Aboriginal People: Eastern Woodlands and general articles under Aboriginal People.