In 1770 George Washington came to this area to inspect lands awarded to him by Virginia for his military services. After the Revolutionary War, Blennerhassett Island, in the Ohio River west of Parkersburg, was the scene of the alleged Burr-Blennerhassett plot. Harman Blennerhassett, a wealthy Irishman, built a lavish mansion on this island. After killing Alexander Hamilton in a duel, Aaron Burr came to the island, allegedly with the idea of seizing the Southwest and setting up an empire; Blennerhassett may have agreed to join him. On December 10, 1806, the plot was uncovered. Both men were acquitted of treason but ruined financially in the process. The Blennerhassett mansion burned in 1811 but was later rebuilt.

Today Parkersburg is the center for many industries, including glass, chemicals, petrochemicals, and ferrous and other metals. Fishing is popular in the area, especially below the Belleville and Willow Island locks and dams on the Ohio River.