The exact number of interments in Old City Cemetery is unknown because of a lack of official records before 1914, but it is estimated that 18,000–20,000 people are at final rest there.

They represent an unusually diverse cross-section of the local community, including founding fathers and mothers of the town, Confederate soldiers who died in military hospitals, African American tobacco factory laborers, European immigrants, paupers, and "strangers" who died passing through town.

In fact, at that time it was the only burial ground, excluding private family graveyards, available to African Americans in the area.

A notable burial is that of Ota Benga (c. 1883–1916), a Congolese pygmy exhibited at human zoos, although his remains may have been later moved to Lynchburg's White Rock Hill Cemetery.

The 27-acre (11 ha) site includes four small historic house museums located inside the cemetery, which is cared for by the Southern Memorial Association.