Grafton National Cemetery was authorized in 1865 when Congressman Swinton Burdett of Iowa introduced a bill creating a National Cemetery in northern West Virginia. As commander-in-chief of the Grand Army of the Republic, a Union veterans organization, Burdett had toured Civil War battlegrounds of the area, and wished to establish a common cemetery for war dead. After Congress approved the bill, the War Department located a site accessible to railway lines, reasonably level, and in close proximity to battlegrounds, military hospitals, and other cemeteries.

Work began in 1867 on the 3.21-acre site purchased from the heirs of Alexander Yates. Within two years, 1,251 Union and Confederate troops, including 664 unknown soldiers, were reburied in the cemetery under the supervision of the U.S. Burial Corps. The original bodies interred at Grafton represented war dead from 32 West Virginia counties and 14 states. The first casualty of the Civil War, West Virginian Thornsberry Bailey Brown, is buried in the cemetery, his grave marked by a special monument.

The cemetery reached its capacity of 2,119 graves in 1961. In addition to Civil War casualties, veterans of the Spanish-American War, World Wars I and II, Korean War, and Vietnam War are buried on the cemetery's three terraces.

West Virginia National Cemetery, a separate cemetery five miles outside Grafton, was dedicated in 1987.

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