North Santee is a census-designated place in Clarendon County, South Carolina, United States. It was first listed as a CDP prior to the 2020 census with a population of 749. The CDP is on the southwestern edge of Clarendon County, on the northeast shore of Lake Marion, a reservoir on the Santee River. Interstate 95 crosses Lake Marion at North Santee, with access from Exit 102. U.S. Routes 15 and 301 pass through the CDP as a surface highway, joining I-95 at Exit 102 to cross the lake.