Located in the Northern Panhandle of West Virginia, Brooke County is bounded on the north by Hancock County, on the south by Ohio County, by Pennsylvania on the east, and by the Ohio River and the state of Ohio on the west. The surface of Brooke County is mostly high rolling land, cut in every direction by deep ravines, along which flow rivulets and brooks. Most of Brooke's streams merge into Harmon, Buffalo, Cross, and Short creeks, and all drain west to the Ohio River. Bottomlands of varying widths border the Ohio.

At 92.8 square miles, Brooke is among the smallest counties in the state. Its average width is about seven miles and its length about 16 miles. The population in 2020 was 22,559. Wellsburg, the county seat, is located on the Ohio River at an elevation of 635 feet above sea level. Brooke County is divided into five magisterial districts: Buffalo, Wellsburg, Cross Creek, Follansbee, and Weirton. The county's municipalities are Bethany, Follansbee, Weirton (part of which is also in Hancock County), Wellsburg, Beech Bottom, and Windsor Heights.

Brooke County was established under an act of the General Assembly of Virginia, passed November 30, 1796. The first county court meeting was held in Wellsburg, known as Charlestown at the time, on May 23, 1797. The county was formed from part of Ohio County and named in honor of Robert Brooke, governor of Virginia (1794-96). Brooke County was the 11th county created in the area that was to become West Virginia. It extended to the northernmost tip of the panhandle until 1848, when Hancock County was created from the northern half of Brooke.

Although there was Indian activity in the county, not much has been recorded. Richard "Greybeard" Wells erected a fort in northeastern Brooke County and maintained good relations with the natives. In contrast, in 1774, Daniel Greathouse and Joseph Tomlinson plus about 30 others massacred all of an Indian encampment, except for a little girl they kept as a prisoner. The dead were of Chief Logan's family and tribe, including Logan's sister. Logan, who bitterly memorialized the event in his famous speech, retaliated in a bloody campaign against settlers of European descent, a precipitating factor in Dunmore's War.

Three prehistoric mounds were located at Beech Bottom, and one was found in what is now Follansbee. The last European-American man killed in Brooke County by the Indians was John Decker.

Indian trails, military roads, and the Ohio River served Brooke's early transportation needs, and by the 1870s the Pennsylvania Railroad's main line crossed east to west through Brooke County, on its way to St. Louis. The north-to-south Panhandle Railroad (now gone) made its first run February 28, 1878. Today, the county is served by two railroads. Brooke is also served by State Route 2, a main highway which parallels the Ohio River; State Routes 27 and 67, which cross the county from the east and join Route 2 at Wellsburg on the west; U.S. 22, going east and west at the county's northernmost boundary; plus State Route 88, beginning at State Route 27 and going south to Wheeling.

Brooke County is situated in the busy Ohio Valley. Between 1790 and the 1850s, the principal activities were agriculture, small specialty industries, some mining, and transportation. Gristmills ground local grain, and flour became a leading product, shipped on the Ohio River to New Orleans and elsewhere. The glass industry has one of the oldest continuous histories, beginning in the county in 1813. Coal mining started on a relatively small scale in the late 19th century and boomed in the 20th century, changing the face of the county. Coal, the river, and available flat bottomland brought steel, electricity, and chemicals to Brooke County. Today Brooke produces sheet metal and tin containers, plastic containers, coal, paper bags, tar and chemicals, electric power, glass and glassware, dairy products, and fruit. Sheet steel and tin plate plants and allied industries are located at Beech Bottom and Follansbee.

The Brooke County public library is in Wellsburg, with a branch in Follansbee. Brooke County's historical museum is in Wellsburg, housed in a structure built in 1795. There are four primary schools, a middle school, and one consolidated high school. In addition to these public schools, there are also two parochial schools. The county is home to Bethany College, which was established in 1840 by Alexander Campbell, a theologian, author, and founder of the Christian Church (Disciples of Christ). Two of West Virginia's 17 National Historic Landmarks are located at Bethany, the Campbell Mansion and Old Main at Bethany College.

Today there are more than 35 churches representing 21 denominations in Brooke County. St. John's, the first Episcopal church west of the Allegheny Mountains in what is now West Virginia, was erected on the Follansbee and Eldersville Road in 1793. An 1849 church building serves the congregation today.

In 2022, Follansbee's longtime coke-making plant, once owned by Wheeling-Pittsburgh Steel, permanently closed. In 2023, Brooke County's largest employers were Weirton Medical Center, the county school system, Walmart, WMC Physician Practices, and Justrite Manufacturing.

For recreation, Brooke Hills Park offers fishing, swimming, golf, picnic shelters, games, and hiking. Castleman Run Lake, Cross Creek, Buffalo Creek, Short Creek, and the Ohio River are all popular with fishermen. Boating, speedboating, and water skiing draw many to the river, which is also a major commercial waterway. There is also the Highland Springs golf course. Community parks offer swimming, soccer, hockey, and other activities.

Brooke County has a long and proud past, with many old family names still represented in the area. Efforts are being made to preserve the past for the future. A high percentage of the county's structures were constructed in the 1800s, and some are still standing from the 1790s, leading one to believe that those who built here intended to stay for a long time.