Wellsburg is the county seat of Brooke County. It is situated in the Northern Panhandle on the Ohio River. The town is 16 miles north of Wheeling and 40 miles west of Pittsburgh, at an elevation of 661 feet. It is served by state routes 2, 27, and 67.

Wellsburg has one primary school and one middle school, with the county's consolidated high school nearby. There are also a parochial school and an alternative learning center. Brooke County Public Library is located in Wellsburg. The town has a volunteer fire department, several banks, and one weekly newspaper. There are churches of various denominations. The diverse economy includes two paper mills, a glass gift outlet, several telemarketing facilities, and a factory that does metal fabrication plus plastics molding.

In 1772, the Cox brothers, Friend, Israel, and Jonathan, made tomahawk claims in the area now including Wellsburg. Their claims totaled 1,200 acres. In March 1788, Charles Prather purchased 481 acres from the Cox heirs for $3,000. In 1791, Prather petitioned Ohio County to incorporate the town of Charlestown, Virginia, naming it after himself. The original name continued until 1816, when it was changed to Wellsburg, to avoid confusion with Charles Town, Jefferson County. The new name was in honor of Alexander Wells, Charles Prather's son-in-law. Late in 1890, nearby Midway and Lazearville were annexed to Wellsburg.

The city’s population peaked at 6,398 in 1930. The closing of factories led to a significant decline beginning in the 1960s. In 2020, the population was 2,455, making it West Virginia’s 51st largest city.

Wellsburg was the home of Patrick Gass, the last surviving member of the Lewis and Clark expedition and author of a memoir of the famous journey. Here also was the home of Joseph Doddridge, author of Notes on the Settlement and Indian Wars. The original Grimes Golden apple tree was found just east of Wellsburg. The first glass factory in Western Virginia was built at Wellsburg in 1813.

The Wellsburg Wharf was added to the National Register of Historic Places in 1979 and the historic district in 1982.

Read the National Register of Historic Places nomination for the Wellsburg Wharf.

Read the National Register of Historic Places nomination for the Wellsburg Historic District.