North Santee is a census-designated place (CDP) in Clarendon County, South Carolina, United States.

[4] 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.

Routes 15 and 301 pass through the CDP as a surface highway, joining I-95 at Exit 102 to cross the lake.

Santee Indian Mound and Fort Watson is a historic site in the north part of the CDP, near the shore of Lake Marion.