Murfreesboro is located in northwestern Hertford County on high ground south of the Meherrin River.

[10] The first known deed to property in the area is a land grant dated November 5, 1714, made to Henry Wheeler for a tract on the Meherrin River which included what is now Murfreesboro.

On May 27, 1746, James Jordon Scott sold 150 acres (0.61 km2) on the Meherrin River (part of Wheeler's original grant) to an Irish immigrant, William Murfree from Nansemond County, Virginia.

[9][11] This act also provided for the establishment of a public dock, as the town was located at the northernmost point of navigation on the Meherrin River.

[9] Murfreesboro was designated by the US Congress in 1790 as an official port of entry, and the customs records indicate a profitable three-cornered trade with New England and the West Indies.

[citation needed] In 1809, the Hertford Academy was established in Murfreesboro, opening in 1811 for male students.

[12] In 1831 Murfreesboro was among towns that sent armed forces (these were led by Captain Solon Borland) to Southampton County, Virginia, to quell Nat Turner's slave rebellion.

The last commercial vessel to operate on a regular basis was a Texaco Oil barge; it ceased service to the town in October 1966.