The west terminus of South Carolina Highway 290 is with its junction with US Highway 25 approximately halfway between Travelers Rest and Tigerville. It generally follows a southeast route through the small villages of Locust Hill and Sandy Flat before entering Greer. Within Greer, its course changes to an easterly direction and it continues over the county border into Spartanburg County. SC 290's course changes back to a southeasterly direction as it passes through Duncan. It then crosses Interstate 85 at exit 63 and continues on until it reaches its east terminus, the junction with US Highway 221, in Moore.