The State Board of Health was established by the West Virginia legislature in 1881, with an annual budget of $1,000. By 1890, local health boards had been established with health officers instructed to place warning placards on residences to control smallpox, scarlet fever, measles, and diphtheria, the leading causes of death at that time. Early effects of the state board included the establishment of hospitals for the mentally ill at Spencer (1893) and Huntington (1897) and the construction of Miners Hospitals in Welch, Fairmont, and McKendree after 1899.

In 1908, responding to a worldwide epidemic, the Board of Health recommended that West Virginia make provision for the care and treatment of tuberculosis. The state's first tuberculosis sanitarium was founded in 1913 at Hopemont in Preston County; Denmar Sanitarium for black tubercular patients was established in Pocahontas County in 1917. Pinecrest, also a TB sanitarium, opened in Beckley in 1930. Significant advances in public health were made during the administration of Governor Hatfield (1913—17), himself a medical doctor. The State Department of Health was established in 1915, replacing the Board of Health.

Smallpox was among the world's worst diseases until well into the 20th century, highly contagious and often fatal. West Virginia was not spared. In 1906, 19 cases of smallpox were reported in Hampshire County within a radius of four miles. Quarantine had not been properly enforced due to a difference of opinion regarding the diagnosis. In 1903, the death rate from smallpox was reported as being from 12 to 20 percent of reported cases. The Board of Health recommended that authorities urge everyone to be vaccinated, and revaccinated at every remotely suspected exposure to the disease. In 1927, 1,099 cases of smallpox were reported. The last case of smallpox was reported in 1948.

The Division of Vital Statistics was established by the West Virginia Legislature in 1917. This was a first attempt to centralize the registration of births and deaths. It was done on a cooperative basis because the law did not require reporting of this information to the state until 1921. Prior to 1921, physicians, midwives, and undertakers were required to report births and deaths only to the clerk of the county courts of the county in which the event occurred.

The state received a federal grant for the control of venereal disease in 1919. Funding for maternal and child health began in 1921, along with the collection of vital statistics. The first nutrition campaign was discussed and the state's milk control program began, both in 1927.

Statewide distribution of Salk polio vaccine began in 1953 as a step toward the prevention of paralytic poliomyelitis following a year when 21,000 new cases were reported nationally. The Division of Disease Control with the assistance of a federal grant, began a statewide polio vaccination program in 1957. Salk vaccine was administered to persons up to 20 years of age and to expectant mothers. This proved to be a turning point in the fight against this crippling disease. The last case of polio in West Virginia was reported in 1968.

Today, local health departments protect environmental health from risks associated with drinking water, sewage and wastewater, and food and milk sanitation. They offer disease prevention and control, responding to epidemics, rabies, tuberculosis, and sexually transmitted diseases, including AIDS. They address community health problems like tobacco use and physical inactivity. Some health departments offer clinical services including prenatal, family planning, breast and cervical cancer, immunizations, pediatrics, nutrition, home health, and primary care.

The West Virginia Public Health Association, an affiliate of the American Public Health Association, was organized in 1924. Members include nurses, sanitarians, physicians, dentists, health educators, laboratory technicians, clerks, administrators, epidemiologists, biostatisticians, nutritionists, outreach workers, academics, and retirees. Public health practitioners are trained at West Virginia University through the Master of Public Health degree offered by the Department of Community Medicine. The accredited program is offered statewide via distance learning and the teaching of adjunct faculty.

Public health in West Virginia is overseen by the West Virginia Bureau for Public Health. Services are provided in all 55 counties and in larger cities through local health departments. The total budget is $150 million. The demand on these funds is substantial. Entering the 21st century, West Virginia is one of the least healthy states. The leading causes of death are heart disease, cancer, diabetes, stroke and lung disease. West Virginia exceeds national figures in smokeless tobacco use, physical inactivity, obesity, hypertension, and cigarette smoking.