Administered by the United States Department of Veterans Affairs, it encompasses 29.6 acres (120,000 m2) of land, and as 2021, had over 14,000 interments.

During the American Civil War, the territory around the city of Culpeper was defended vigorously by both sides, as it was a strategic point almost exactly between Washington D.C. and the capital of the Confederacy, Richmond, Virginia.

After the war a reburial program was initiated, and in 1867, Culpeper National Cemetery was established to reinter many of the remains from the makeshift sites.

These make-work improvements included replacing the original 1870s tool house at the cost of $8,000 in 1934, raising and realigning 912 headstones in May 1934, by the Civil Works Administration, and realignment and re-setting 402 headstones in 1936 though a Works Project Administration project.

American Nazi Party founder George Lincoln Rockwell, who had served in the US Navy until his discharge in 1960, was to be buried at the cemetery after his assassination in 1967 but the cemetery refused to inter him after neo-nazis who attended the service displayed Nazi insignia.