Organized in 1773 as Eno Meeting House, this was one of the earliest congregations established in what became Durham County. As documented by Jean Bradley Anderson, the will of Richard Rhodes and property records from Orange County as far back as the 1790s indicate land at this same location was set aside for this purpose. The name of the congregation changed at some point in the 19th century, though it is unclear if that reflects a change in its affiliation. Newspaper references dating to 1840 make it clear that the church was affiliated with Baptist conventions by that time, while the present name - Eno Primitive Baptist Church - has been in use since at least the 1880s.
The earliest log structures on this site are said to have burned and been replaced prior to the Civil War. Some portion of the present, brick-veneered structure - modified as recently as 1976 - is believed to date to that era.
Included in over four acres of church property between Danube Lane and Old Oxford Road is also one of the county's oldest continuously operating cemeteries. Cemetery Census suggests it contains the graves of many enslaved people and their descendants - perhaps indicating African Americans were members of the congregation prior to Emancipation. Indeed, this seems to be one of relatively few burial grounds in which both White and Black Durhamites rest side-by-side (albeit apparently in segregated sections).