Wheeling stands on the site of Fort Henry, built in 1774 by Colonel Ebenezer Zane and his two brothers, who named the fort for Virginia's Governor Patrick Henry. In 1782 the fort was the scene of the final battle of the Revolutionary War, a battle in which the valiant young pioneer Betty Zane was a heroine. The fort had withstood several Native American and British sieges during the war. However, during the last siege (after the war was officially ended), the defenders of the fort ran out of powder. Betty Zane, sister of the colonel, volunteered to run through the gunfire to the outlying Zane cabin for more. With the powder gathered in her apron, she made the 150-yard trek back to the fort and saved the garrison. Zane Grey, a descendant of the Zanes, wrote a novel about Betty and her exploit.

Today Wheeling is home to many industries, including producers of steel, iron, tin, chemical products, pottery, glass, paper, tobacco, plastics, and coal.