Frontier heroine Elizabeth "Betty" Zane, born in the present Eastern Panhandle about 1760, was credited with saving Fort Henry in Wheeling when it was besieged in 1782, during the Revolutionary War. Conflicting reports claim that Molly Scott actually saved the fort, but Zane's role is generally accepted.

On September 10, 1782, 200 or more warriors, mostly Wyandots and Delaware with some American Loyalists and British, attacked the fort. Inside, 47 patriot civilians and militia held their ground until their gunpowder was exhausted. Betty Zane was the sister of the fort commander, Col. Silas Zane. According to a common account she volunteered to retrieve gunpowder from the Zane family cabin, perhaps as much as 60 yards away. "You have not one man to spare; a woman will not be missed in the defense of the fort," she is quoted as having said. Startled to see a young woman emerge from the fort and sprint across the open field, the British and natives held their fire. In the Zane cabin, Betty gathered a quantity of gunpowder, perhaps in her apron, and dashed back to the fort.

Betty Zane married and moved to Martins Ferry, Ohio, where she died, probably in 1823.

Later the author Zane Grey, a collateral descendant, wrote the 1903 novel Betty Zane based on the incident and related events. Some historians are skeptical of the historical accuracy of Betty Zane's deed, but the legend persists. There is no mention of the heroic act in any contemporary account, including the official report by her brother to Gen. William Irvine. Its similarity to the account of Mad Anne Bailey's dash to save Fort Lee in the same decade casts additional doubt. The earliest reports of the episode are found in A. S. Withers's 1895 Chronicles of Border Warfare and in an early 19th-century Philadelphia newspaper account.