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The first European-American settlement in the Wheeling area was established in 1769 by Ebenezer, Silas, and Jonathan Zane, who moved from the South Branch Valley. They were joined by enslaved people and friends like the Wetzels, Caldwells, Shepherds, and McCollochs.
In 1774, after Chief Logan's family was killed, Indian attacks led to Dunmore's War. Soldiers from Fort Pitt built Fort Fincastle (later called Fort Henry) near Wheeling Creek. The community was attacked in 1777 and 1782 but survived, especially after Betty Zane made a famous run for gunpowder run. In 1796, Ebenezer Zane created a trail to Kentucky, making Wheeling an important hub for pioneers.
