Situated at the confluence of Vandemere Creek and the Bay River, Vandemere is home to many descendants of the first North Carolina colonists. Incorporated in 1874, Vandemere was the first county seat when Pamlico County was formed in 1872 to 1876.

Early settlers came from England along with French Hugenots, the Dutch and Flemish. Records from the late 17th century indicate several spelling variations of Vandemere including Vandermoller and Vandemore.

Native Americans were known as the Bay River Indians.