Slavery never prospered on a widespread basis in the area that became West Virginia. On the eve of the Civil War, the entire Commonwealth of Virginia had an enslaved population of almost a half-million persons. Of these, only a relative handful resided in present West Virginia. In 1850, when the West Virginia section's enslaved population was at its apex, the number was 20,527 or 6.79 percent of the area's total population of 302,313. By 1860, the western section's enslaved population had declined both in number and as a percentage of the whole population.

The enslaved population was concentrated in four Western Virginia valleys: Shenandoah, South Branch, Kanawha, and Greenbrier. In 1850, only seven counties had more than 10 percent of their total population in slaves. These seven counties had 70.77 percent of all slaves in the West Virginia section of Virginia. In 1850, Jefferson County had the largest portion in number (4,341) and as a percentage (28.2) of total county population. Berkeley County had 1,956 slaves, 16.6 percent of its aggregate population. Hampshire County had the most slaves (1,433) in the South Branch region. The enslaved population of Kanawha County numbered 3,140, with most concentrated in Kanawha Salines. Greenbrier County had 1,317 slaves.

The great influx of slaves into the Shenandoah Valley came between 1768 and 1810, when Tidewater Virginians left their depleted tobacco plantations for new lands. These planters became wheat and general farmers and sometimes retained plantation ideals. Slaves with overseers often preceded their owners to clear and fence land and to erect housing. African Americans cleared the forest, split rails, and removed rocks from fields. They also tended the livestock, plowed thousands of acres, harvested the crops, and hauled the produce to storage or market. Slaves supported all aspects of the household and domestic lifestyle, sometimes opulent, of the master and family. Some were skilled craftsmen. Many endlessly cut wood for cooking and for heating the huge houses. They raised, harvested, preserved, and prepared the food, and some took care of children.

The large slaveholders on the fertile South Branch soils of the Eastern Panhandle and on the limestone soils of Greenbrier and Monroe counties emulated to some degree the eastern Virginia or Shenandoah pattern of slave use. Locational and economic differences pushed slaves into occupations associated with a livestock economy and into land-clearing. The spas at western mineral springs often relied on enslaved labor as well.

Throughout the Trans-Allegheny, scattered slaves labored in the domestic service of well-to-do owners. Other owners in this area generally held bondsmen in single or small numbers and worked beside them on farms, in craft occupations, service enterprises, or small manufacturing operations. In the southwest, below and along the Kanawha River, slaves labored along with their masters in labor-intensive tobacco farming. The extensive industrial use of slaves in coal mining and salt manufacturing around Kanawha Valley salt furnaces was atypical.

In 1850, Kanawha saltmakers employed more than 1,500 slaves in all phases of their enterprise. These manufacturers leased more than half of the total number of bondsmen under their control. The leased slaves were usually from eastern Virginia, and some remained most of their lives on the Kanawha. Slaves at the salt furnaces worked as coal miners, teamsters, kettle-tenders, steam engine tenders, salt lifters and wheelers, general laborers, packers, blacksmiths, and cooks. Some slaves were foremen. Several saltmakers also used slaves as farmers to feed their furnace laborers.

In areas of military activity, the Civil War loosened the bonds of slavery's control, allowing slaves freedom and unlimited mobility. Bondsmen in remote areas generally remained with their masters and maintained the old relationships and work patterns. Fleeing slaves who remained in the state tended to congregate in towns where they could support each other. Often free persons of color supported refugees. In county seat towns in northern West Virginia, free and enslaved Blacks engaged in a wide variety of trades and in domestic service. On the Kanawha, a greatly reduced number of Blacks continued to mine coal and manufacture salt during the war.

In the Shenandoah Valley, many male slaves fled to Pennsylvania. Some labored for federal forces or enlisted in the Union army. Single Black males often prospered, but the females, children, and infirm remaining on farms frequently experienced great hardship. Some large landowners encouraged the casual formation of Black communities on their land to retain labor in the locality.

Although relatively uncommon in the west, slavery nonetheless greatly influenced Western Virginia's political destiny. From the American Revolution, slavery affected every political question involving the state's sections and furnished the basic source of grievances that eventually split Virginia. Even in the statehood movement, the slavery issue was paramount. Because the Emancipation Proclamation applied only to areas in rebellion against the United States, and thus not to West Virginia, the Willey Amendment, which provided gradual emancipation of most but not all slaves, became a conditional requirement for statehood. A legislative enactment of February 3, 1865, that arose from consideration of ratification of the 13th Amendment actually freed the Mountain State's slaves.