By the mid-18th century, Europeans and Americans of European descent had begun to settle in the territory that eventually became West Virginia, most numerously in the Eastern Panhandle and Potomac Highlands regions. These settlers were primarily of German and Scotch-Irish origins, although there were significant numbers of English and other nationalities, as well. They found no significant Native population, although the Shawnee and other Indian groups traveled and hunted throughout present West Virginia.

Slave-holding was not common in most parts of Western Virginia, as the rugged landscape discouraged plantation agriculture. There were local exceptions in the major river valleys, including the Greenbrier, Kanawha, and Ohio valleys, and in the Eastern Panhandle. Extensive industrial slavery was practiced at the saltworks of Kanawha County. After the Civil War, the coal industry began to grow quickly and attracted many African Americans to the new state and a variety of European immigrants, especially from southern and eastern Europe. Many African Americans worked in the coal mines in the southern part of the state, including those in McDowell, Fayette, and Mercer counties.

In the 2020 census, West Virginia’s population had declined by 3.2 percent since 2010, making it one of only three states to lose numbers (the others being Illinois and Mississippi). The nation, as a whole, gained 7.4 percent during the same decade. West Virginia's present racial mix is not diverse by national standards. Most West Virginians reported a single-race background in the 2020 census, with just 4.7 percent reporting more than one race, which is up from 1.5 percent in 2010. Further, in 2020, 89.8 percent reported their race as white, down from 93.9 percent in 2010. In 2020, only 3.7 percent reported their race as African American (up from 3.4 percent in 2010), and 0.8 percent reported their race as Asian (a slight increase). Nationally, residents reporting their race as African American and Asian accounted for 12.4 percent and 6.0 percent of the population, respectively.

The state's population has grown older during the last 100 years. According to the 2020 census, West Virginia's median age, at 42.7 years, was higher than the nation's, at 38.31 years. West Virginia has not always had a higher median age than the nation. Indeed, West Virginia's median age was below the national average in 1950 at 26.3 years, compared to the national median of 30.2 years, and in 1900 at 20.3 years, compared to the national median of 22.9 years. The state's current high median age arose in large part from a massive out-migration of relatively young residents during the economic downturn that began in the 1980s. Median age varies in different regions of the state, with the northwestern and southeastern areas of the state registering the highest. The counties in the Eastern Panhandle and the southwestern part of the state recorded the lowest. Monongalia County had the lowest median age in the state, at 32.2 years, reflecting the college student population at West Virginia University. Pendleton County had the highest median age, at 51.8 years. Monongalia County was the only county in West Virginia with a median age below the U.S. average. The state's age structure negatively affects the rate of natural increase, which is a major component of population growth. Natural increase is the annual difference between births and deaths. During the 2000s, births roughly equaled deaths in West Virginia. This is unusual, and indeed, the state has lately posted the lowest rates of natural increase of any state in the nation. The low natural increase has arisen because of low birth rates combined with high death rates. Both rates are attributable in part to the state's high median age, since an older population naturally has fewer births and more deaths. However, it turns out that even when adjusted for age, West Virginia's residents still have low birth rates (especially for women after their mid-20s) and high death rates.

West Virginia's demographic composition does not favor population growth. The state's residents are overwhelmingly white (whites have lower birth rates than Blacks and Hispanics, the other most numerous elements in the U.S. population) and tend to be near the end of their child-bearing years. These characteristics produce low rates of natural increase. This, in turn, makes the state dependent on net migration (the annual difference between those moving into the state and those leaving) for overall population gains. Success in generating more in-migrants than out-migrants often requires strong economic performance, which has proven difficult for West Virginia in recent decades.