Rich in history and natural resources, Greenbrier County is the fifth-oldest and second-largest county in West Virginia. Formed during the Revolutionary War, March 1, 1778, from portions of Botetourt and Montgomery counties, Greenbrier County is named for the Greenbrier River. Now composed of 1,024.8 square miles in the southeastern portion of the state, its borders once stretched to the Ohio River, encompassing many other counties in present West Virginia. The county seat is Lewisburg.

The topography is rugged in the west with rolling valleys farther east. Greenbrier County is barricaded on its eastern border by a high range of the Allegheny Mountains, separating the county from neighboring Virginia. Grassy Knob in the northwest has the highest elevation, at 4,360 feet, and the lowest point is near Alderson, at 1,550 feet. This provides a surface relief within the county of nearly 3,000 feet and some of the finest scenery in the Mountain State. Greenbrier State Forest and a portion of Monongahela National Forest occupy parts of the county.

A vast system of limestone caves lies beneath the fertile soil. With 1,199 caves of all sizes, Greenbrier has far more caves than any other West Virginia county, including 412 caves over 33 feet in length. Organ Cave, near Ronceverte, is one of the oldest-known and most famous caves in West Virginia and was the center of a thriving saltpeter mining industry prior to the Civil War.

Agriculture is important in Greenbrier County, which has more than 184,000 acres of farmland. The West Virginia State Fair is permanently located at Fairlea, near Lewisburg.

Historically, lumber and coal have been among Greenbrier's other important industries. The Meadow River Lumber Company, organized in 1910 in Rainelle, was once the site of the largest hardwood manufacturing plant in the world. Poplar, oak, and maple were among the native woods processed at Meadow River. Coal mining boomed in parts of the county early in the 20th century. Some surface mining continues today but on a very small level. In 2021, only 80 Greenbrier Countians worked in the coal industry.

Natural springs appear throughout the county, with several of them supporting thriving resorts in the 19th and early 20th century. Blue Sulphur Springs and White Sulphur Springs drew visitors from a wide region. The Blue, as it was called, was burned during the Civil War by Union troops and later suffered by not being on a rail route. The Old White at White Sulphur Springs fared much better and today is succeeded by the Greenbrier, a world-class resort that continues the tradition of grand hospitality.

By 1820, the population of Greenbrier County was 7,340 inhabitants. Families who settled on the frontier here found rich land and abundant game, and fierce adversaries in the Indians who raided from the Ohio Valley. The frontier defense system, including Forts Donnally, McCoy, and Renick, offered some protection to settlers.

Although life was at first not easy, by 1820 Lewisburg and the Greenbrier Valley had become an established gateway to the new western frontiers of Kentucky, Ohio, and Indiana. One writer of the period said that the James River & Kanawha Turnpike, now U.S. 60, was a "bustling parade of settlers moving west, tinkers, gypsies, and people just one step ahead of the sheriff."

During the Civil War, Greenbrier County was for the most part loyal to Virginia and the Confederacy. Strategically located on the James River & Kanawha Turnpike, Greenbrier suffered as armies clashed in battle as they moved through the region. During the May 1862 Battle of Lewisburg, Generals Hess and Cook fought in the streets of the town. Guests at the Star Hotel watched from the balcony as the battle unfolded below. In 1863, troops maneuvered in Greenbrier County for the decisive Battle at Droop Mountain, just across the Pocahontas County line. The Battle of White Sulphur Springs took place in August 1863. Robert E. Lee found Traveller, his great war horse, in Greenbrier County.

The first school, Dr. John McElhenney's Lewisburg Academy, opened in 1812. Other early schools included the Williamsburg School, the Ronceverte School, the Bolling School, the Alderson Academy (a predecessor to Alderson Broaddus University), and the Greenbrier Male Academy in Lewisburg.

Two schools became especially important. In 1875, the Lewisburg Female Institute took root in the old Lewisburg Academy building. It would become the Greenbrier College for Women. Across town, a school for young gentlemen opened its doors. It became known as the Greenbrier Military Academy (later Greenbrier Military School) in 1890 and closed in 1972. Today its campus is the home of the West Virginia School of Osteopathic Medicine.

Towns and cities within Greenbrier County include Lewisburg, White Sulphur Springs, Alderson, Ronceverte, Rupert, Rainelle, and Renick. The unincorporated communities include Caldwell, Smoot, Trout, Hart's Run, Asbury, Fort Spring, Frankford, and Williamsburg. Greenbrier County’s population peaked at 39,295 in 1950 and had declined to 32,977 in 2020. In 2023, Greenbrier County's largest employers were the Greenbrier Hotel Corporation, the county school system, Greenbrier Valley Medical Center (CAMC), the West Virginia School of Osteopathic Medicine, and Walmart

Lewisburg, the county seat, was established in 1782 and is among the oldest cities in West Virginia. Known first as "the Savannah" and later as "Camp Union," it was named Lewisburg in honor of Andrew Lewis and the Lewis family. Old Stone Presbyterian Church, the oldest church building in continuous use west of the Allegheny Mountains, is located in the Lewisburg National Historic District, which also includes the 1835 Courthouse, the North House Museum (once the Star Hotel and site of a speech by Henry Clay), Carnegie Hall, and the John Wesley Methodist Church, which still bears the scars of cannonballs from the Battle of Lewisburg.

In 2016, a deadly flood along the Meadow River devastated the towns of Rupert and Rainelle, and Howard Creek raged through White Sulphur Springs and the grounds of the Greenbrier resort.

Samuel Price of Greenbrier County, who voted against secession at the Virginia convention but nonetheless signed the Ordinance of Secession, was lieutenant governor of Confederate Virginia. Three Greenbrier Countians became governors of West Virginia, Henry Mason Mathews, 1877-81, Homer Holt, 1937-41, and Jim Justice, 2017-present. Other notable Greenbrier County natives include World War I generals John Hines and Mason Mathews Patrick. General Hines later served as the U.S. Army chief of staff, from 1924 to 1926. General Patrick, the son of a Confederate surgeon, was chief of the Air Service of the American Expeditionary Force during World War I. He continued to serve as chief of the Army Air Service until 1927.