The highway travels generally north-to-south (but is signed as west–east) across the eastern portion of the state, and is one of the most popular routes to Myrtle Beach.

The road, signed eastbound, heads south through rural unincorporated areas of Marlboro County.

heads directly through the downtown area of the city, SC 38 continues southwest on Oakwood Street.

Shortly after an intersection with SC 385, the road reaches US 15/US 401 and the two state highways form another concurrency with the U.S. routes through a commercial district.

After crossing into Dillon County, the highway heads along the side of a residential neighborhood in the unincorporated community of Oak Grove and reaches Interstate 95 (I-95) at its exit 181.

[4] SC 38 was one of the first highways in the South Carolina state system, originally running from Myrtle Beach through Socastee and Conway to Marion and Latta.

[citation needed] In 2005, highway officials from North and South Carolina met and passed a resolution designating that Interstate 73 would be built along the route of SC 38.

[8] In June 2012, though, Miley and Associates of Columbia, South Carolina recommended improvements to SC 38 and US 501 to create the Grand Strand Expressway (GSX), a position long held by the Coastal Conservation League, which asked for the study.

SC Representative Alan Clemmons, head of the National I-73 Corridor Association, said such a plan had been considered but was not likely.

The route begins running concurrent with SC 9 heading north along Broad Street.