The causes of the American Civil War were varied and complex. Most of the issues at the heart of the sectional conflict, however, can be attributed to the institution of slavery, particularly matters pertaining to the extension of slavery into the western territories of the United States. Events such as John Brown's raid on the U.S. Arsenal at Harpers Ferry in 1859 made a precarious political situation much worse. The Republican Party had taken a stand on the slavery issue and made the non-extension of slavery one of the planks in its platform during the presidential election of 1860. When Republican Abraham Lincoln won the election on November 6, 1860, the states of the Deep South began the process of holding secession conventions.

By the time of Lincoln's inauguration in March 1861, the states of South Carolina, Mississippi, Florida, Alabama, Georgia, Louisiana, and Texas had left the Union. The states of the Upper South had so far either rejected secession or refused to call conventions. Virginia initially rejected secession, but kept its convention in session to see what Lincoln would do. On April 15, three days after Fort Sumter surrendered to Confederate forces, Lincoln called upon the states to supply 75,000 militiamen for three months' service, including troops from the Upper South slave states that had not yet seceded. Lincoln's request for volunteers was the catalyst that caused these states, Virginia included, to join the Confederate States of America.

West Virginia has the unique distinction of attaining its statehood directly because of the Civil War. This region possessed geographic, economic, and settlement patterns that set it apart from eastern Virginia. Issues involving political apportionment, public spending on internal improvements, and slavery exacerbated these differences in the decades preceding the conflict. When the Commonwealth of Virginia seceded from the Union on April 17, 1861, leaders primarily from the northwestern region of the state began the political process that eventually led to the creation of the new state of West Virginia on June 20, 1863.

Though no great battles approaching the magnitude of Gettysburg or Chickamauga were fought on West Virginia soil, the area that became the state of West Virginia nonetheless saw a great deal of military activity during the four years of conflict. Several small but strategically significant early battles, including Philippi and Rich Mountain, were part of Maj. Gen. George B. McClellan's campaign in June—July 1861 to secure the Baltimore & Ohio Railroad and gain control of the western part of Virginia for the Union.

Meanwhile, the process of recruiting men to fill the ranks of Union regiments from (West) Virginia had begun in earnest. By the end of the war, more than 32,000 soldiers had served in West Virginia regiments and other military organizations, although many of these men, probably a third at least, were natives of the nearby states of Pennsylvania and Ohio. The greatest Union sentiment was found in the 24 northwestern counties bordering Pennsylvania, the Ohio River, and along the lines of the Baltimore & Ohio Railroad. Like Maryland, Kentucky, Missouri, and the other border states, the allegiances of West Virginia's citizens were split. The number of Confederate soldiers who came from West Virginia counties numbered in the neighborhood of 18,000. Devotion to different causes resulted in much irregular warfare, with bushwhacking, raids by "partisan rangers," and guerrilla attacks common occurrences throughout the conflict. Towns such as Romney endured repeated occupation by both sides, as citizens witnessed firsthand the cruelties of civil war.

Soldiers from West Virginia fought in most of the large battles of the war. Confederate regiments from what is now the Eastern Panhandle of West Virginia brigaded together with other units from the Shenandoah Valley at First Manassas on July 21, 1861, under command of another native son, Thomas J. Jackson. There, on Henry House Hill, Jackson and his brigade earned the nickname "Stonewall" for their tenacious combat abilities. At Second Manassas in late August 1862, Confederate (West) Virginians in the Stonewall Brigade held their position against overwhelming odds behind the bed of an unfinished railroad. At Antietam, the 7th West Virginia Infantry (U.S.) sustained its highest number of casualties of the war during an attack on a sunken road that forever after was called "Bloody Lane." At Gettysburg, Union troopers in the 1st West Virginia Cavalry took part in a fruitless cavalry charge against Confederate infantrymen on July 3, 1863, during the waning moments of that great battle. That same day (West) Virginia Confederate soldiers in Gen. George Pickett's Division assaulted the center of the Union line on Cemetery Ridge, while artillerymen in Battery C, 1st West Virginia Light Artillery did their best to stop them. Hundreds of miles to the southwest of Gettysburg, seven soldiers of the 4th West Virginia Infantry were awarded the Medal of Honor for heroism in a Union assault on the Vicksburg defenses.

The largest military engagements fought within the present-day borders of West Virginia were at Harpers Ferry and Shepherdstown in September 1862, Droop Mountain in 1863, and Summit Point in 1864. Numerous smaller actions also were fought at places such as Scary Creek, Cheat Mountain, and Carnifex Ferry (1861); Lewisburg (1862); Bulltown (1863); and Charles Town (1864). Many of these smaller actions were fought between Union and Confederate soldiers who were West Virginia natives.

Large numbers of soldiers from West Virginia fought opposite each other, especially during the Shenandoah Valley campaigns of 1862 and 1864. For example, at the Battle of New Market on May 15, 1864, Union soldiers of the 1st and 12th West Virginia Infantry, supported by the cannons of batteries D and G, 1st West Virginia Light Artillery, encountered Confederates from the 22nd Virginia Infantry Regiment, recruited in the Kanawha Valley and commanded by Col. George S. Patton of Charleston. Several other Confederate units that fought at New Market were composed of West Virginians, and some of the cadets serving in the Virginia Military Institute battalion came from West Virginia.

When the Confederate armies surrendered in the spring of 1865, West Virginians of both the Blue and the Gray returned to their new state. Years later, when West Virginia Union veterans became eligible for federal pensions and Confederate veterans received pensions from their state governments, the West Virginia ex-Confederates again were on the losing side: West Virginia would not recognize their service, and the Commonwealth of Virginia would provide pensions only to its own residents. Today, the fratricide of the Civil War is symbolized on the grounds of the West Virginia state capitol, where a statue honoring West Virginia's Union soldiers stands in silent counterpoint to a statue of Stonewall Jackson, with Abraham Lincoln brooding between the two.