It generally follows a southeast route through the small villages of Locust Hill and Sandy Flat before entering Greer.
SC 290's course changes back to a southeasterly direction as it passes through Duncan.
It then crosses Interstate 85 (I-85) at exit 63 and continues on until it reaches its east terminus, the junction with US 221, in Moore.
Just before an intersection with the southern terminus of Ashmore Street, the roadway begins to curve to the east-southeast.
Immediately, they have an interchange with SC 290 (East Poinsett Street Extension).