Charles Wells settled Sistersville in the early 19th century. In 1839 the town was incorporated and named in honor of his daughters, Sarah and Deliah, the 18th and 19th of his 22 children.

Sistersville's relatively quiet posture as a farming and trade community on the Ohio River, changed dramatically in 1889 with the discovery of oil on an area farm. Oil barons descended upon the town, building unsightly rigs as well as many stately homes and a striking business district along Wells Street. The oil boom ended in 1915, returning the town to its earlier lifestyle, but leaving the handsome historical buildings.