Ohio County, located in the Northern Panhandle of West Virginia, was created in 1776. It was one of the first counties in Virginia west of the Allegheny Mountains and, with Monongalia and Yohogania, one of the three counties formed from the District of West Augusta. Yohogania County was dissolved when the Virginia-Pennsylvania border dispute was settled in 1784, and thereafter Ohio County had all of the present Northern Panhandle and neighboring areas to the south. Other counties were later carved from its territory, including Brooke, Hancock, Marshall, Tyler, and Wetzel.

Once covering 1,432 square miles, today Ohio County covers 108.9 square miles. It is bordered by Brooke County to the north, Pennsylvania to the east, Marshall County to the south, and the Ohio River to the west. The river has long been crucial to the economy of the area. It is open year-round for navigation and provides transport for millions of tons of cargo through the Wheeling area.

Wheeling is by far the largest community (27,062 in 2020) in Ohio County, followed by Bethlehem (2,605) and West Liberty (1,157). The county's people are predominantly White, with minorities making up less than 6 percent of the total population. Nonetheless, Ohio County has a rich ethnic and religious diversity, the heritage of massive immigration in the late 19th and early 20th centuries.

The topography is generally hilly. Wheeling Creek, together with the smaller Short Creek and Little Wheeling Creek, all drain to the Ohio River. The Pittsburgh coal seam, which underlies Ohio County and a wide surrounding region, is the richest natural resource.

Ohio County was organized at a meeting of the landholders in December 1776, to elect the administrators and select a seat for the court. They chose Black's Cabin on Short Creek, the present site of West Liberty. One of the first orders of business was to lay out a road from Fort Henry (Wheeling) to present Elm Grove, six miles. Because of the unstable conditions brought on by the American Revolution and associated Indian warfare, the court did not meet from June 1777 until April 1778.

Early in the Revolutionary period Black's Cabin was renamed West Liberty to celebrate the love of liberty of those first pioneers. In 1779, a courthouse was completed at West Liberty. Construction was begun on a more substantial courthouse in 1796.

By this time Wheeling was growing as a transportation and commercial center and agitating for the relocation of the county seat. Wheeling won out, and the court was moved to that city December 27, 1797. In June 1798, it was decided to erect a courthouse with a jail, stocks, and whipping post in the vicinity of present 10th Street. This small structure was used until a new building was authorized in 1836, to be constructed at the southeast corner of 12th and Chapline streets. This served as the courthouse until the former state capitol was acquired for use as a courthouse in 1885. The present seat of government is the City-County Building, dedicated in 1960 on the same site as the old state capitol.

The histories of Ohio County and Wheeling are closely interrelated. In 1749, the French expedition under Celoron de Blainville had landed at Wheeling Creek and claimed the site for their king, but the French and Indian War invalidated that claim. The first people of European descent to settle in the area were the Zane brothers who visited the region in 1769 and brought their family and friends from the South Branch Valley of the Potomac River. Because of its strategic location, the community grew quickly. In 1774, the British constructed a fort at the site, Fort Fincastle, later changed to Fort Henry to honor Patrick Henry.

With peace restored in the 1780s, the county again flourished. In 1818 the National Road terminated at Wheeling; in 1849 the suspension bridge was completed over the Ohio; and in 1853 the Baltimore & Ohio Railroad reached the city. The grouping of railroad, National Road, and river ensured Wheeling's growth and prosperity during the long Victorian era.

During the Civil War, Ohio County had divided loyalties. Some of the old families continued their allegiance to Virginia and sent their sons to the Confederate Army, while many others fought for the Union. In 1861, the loyal Reorganized Government of Virginia was founded at the Wheeling Custom House. While there was no fighting in the area, Camp Carlisle on Wheeling Island was a major army recruiting and training center from 1861 to 1865. Our state was born at the Custom House in Wheeling, later known as West Virginia Independence Hall, and in 1863 the first state capitol was located in the city.

Ohio County and especially Wheeling continued their industrial preeminence after the Civil War, manufacturing nails, calico, beer, and cigars, among other products. Coal mining expanded in the rural countryside. Steel established itself as the region's major industry at the turn of the 20th century, with Wheeling Steel (later Wheeling Pittsburgh Steel) founded in 1920.

Today, Ohio County is known for its outstanding public school system. The county is also home to a business college and a parochial school system, as well as Wheeling Country Day School and Linsly schools. Three institutions of higher learning are located in the county: West Liberty University, West Virginia Northern Community College, and Wheeling University. The Ohio County Public Library has served its patrons since 1882.

Ohio County has two fine parks: Wheeling Park and Oglebay. The Oglebay winter Festival of Lights draws thousands to the area each year. The Oglebay Institute is the largest private arts organization in West Virginia and the oldest arts council in the nation. The Wheeling Symphony Orchestra is the oldest in the state.

Ohio County's industrial economy peaked in the first half of the 20th century. As in some other parts of West Virginia, the population declined in later decades, from a high of 73,115 in 1940 to an estimated 42,425 in 2020. Efforts have been made to diversify the local economy. The Highlands, located seven miles east of Wheeling along I-70 in Triadelphia, is a massive shopping, dining, and entertainment complex, with more than 1.4 million acres of retail space.

In 2023, Ohio County's largest employers were WVU Medicine, the county school system, Williams Lea, Wheeling Park Commission, and Tunnel Ridge.

Many important West Virginians have called Ohio County home, from baseball stars Jesse Burkett and Jack Glasscock to opera singer Eleanor Steber, writer Rebecca Harding Davis, and football player Chuck Howley.