There is one truck route and one alternate route in South Carolina.
U.S. Route 221 (US 221) is a 734-mile-long (1,181 km) spur of U.S. Route 21. It travels from Perry, Florida, at US 19/US 98/US 27 Alternate to Lynchburg, Virginia, at US 29 Business. It travels through the states of Florida, Georgia, South Carolina, North Carolina, and Virginia. It travels through the cities of Valdosta, Georgia; Spartanburg, South Carolina; Marion, North Carolina; Roanoke, Virginia; and Lynchburg, Virginia.
U.S. Route 176 is a spur of US 76 in the U.S. states of North Carolina and South Carolina. The U.S. Highway runs 237.98 miles (382.99 km) from US 25 Business and North Carolina Highway 225 in Hendersonville, North Carolina, east to US 52 in Goose Creek, South Carolina. US 176 serves the transition region between the Blue Ridge Mountains and Foothills of Western North Carolina and the Upstate, Midlands, and Lowcountry regions of South Carolina. The highway passes through and connects Spartanburg, one of two major cities in the Upstate, and Columbia, the South Carolina state capital and central city of the Midlands. US 176 parallels and serves as a secondary highway to Interstate 26 (I-26) except for between Spartanburg and Columbia, where the U.S. Highway deviates from the I-26 corridor to serve Union.
U.S. Route 378 (US 378) is a spur of US 78 in the U.S. states of Georgia and South Carolina. The U.S. Highway runs 234.30 miles (377.07 km) from US 78, Georgia State Route 10 (SR 10), SR 17, and SR 47 in Washington, Georgia, east to US 501 Business in Conway, South Carolina. US 378 connects the Central Savannah River Area in both states with the Midlands and Pee Dee regions of South Carolina. The U.S. Highway's western portion, which connects Washington and Lincolnton in Georgia and McCormick, Saluda, and Lexington in South Carolina, is mainly a rural highway. US 378 is a major suburban and urban highway through Lexington and South Carolina's state capital, Columbia. The highway has a lengthy concurrency with US 76 between Columbia and Sumter and serves as a major route between the Midlands and the Myrtle Beach area, between which the highway has a business route through Lake City.
South Carolina Highway 9 (SC 9) is a 259.570-mile (418 km) major state highway in the U.S. state of South Carolina. The highway travels from Cherry Grove Beach to the North Carolina state line upstate. The highway is currently the longest state highway in South Carolina. It is signed as a north–south highway, even though it travels in an east–west direction.
South Carolina Highway 6 (SC 6) is a 116.092-mile (186.832 km) primary state highway in the U.S. state of South Carolina. It extends from US 76 in Ballentine to US 52/SC 6 Truck in Moncks Corner. It uniquely links all three of the major hydropower projects in South Carolina: Lake Murray, Lake Marion, and Lake Moultrie.
South Carolina Highway 34 (SC 34) is a 185.930-mile (299.225 km) primary state highway in the U.S. state of South Carolina. As one of the longer state highways, it traverses the state east-west from Greenwood to Dillon, connecting the cities of Newberry, Winnsboro, Camden, Bishopville and Darlington.
South Carolina Highway 11 (SC 11), also known as the Cherokee Foothills Scenic Highway, is a 119.850-mile (192.880 km) state highway through the far northern part of the U.S. state of South Carolina, following the southernmost peaks of the Blue Ridge Mountains. The route is surrounded by peach orchards, quaint villages, and parks. It is an alternative to Interstate 85 (I-85) and has been featured by such publications as National Geographic, Rand McNally, and Southern Living.
U.S. Highway 29 (US 29) is a 110.202-mile (177.353 km) north–south United States Numbered Highway that travels from the Savannah River to Blacksburg, entirely in Upstate South Carolina.
South Carolina Highway 14 is a state highway in the U.S. state of South Carolina. The state highway runs 59.24 miles (95.34 km) from U.S. Route 76 Business in Laurens north to Interstate 26 (I-26) in Landrum. SC 14 connects Laurens and Landrum with Greer, the city between Greenville and Spartanburg where the highway crosses I-85 and US 29. The highway also parallels I-385 through Fountain Inn and Simpsonville, South Carolina in southeastern Greenville County. SC 14 is a part of the National Highway System between I-85 and US 29 in Greer.
South Carolina Highway 101 (SC 101) is a 56.522-mile (90.963 km) state highway in Laurens, Spartanburg, and Greenville counties in the U.S. state of South Carolina. Its southern terminus is at an intersection with U.S. Route 76 (US 76) in Hickory Tavern, and its northern terminus is at an intersection with SC 11 near Landrum.
South Carolina Highway 290 (SC 290) is a 30.582-mile (49.217 km) state highway in the northwestern part of the U.S. state of South Carolina. It courses through central Greenville and Spartanburg Counties.
Several special routes of U.S. Route 221 exist. In order from south to north they are as follows.
South Carolina Highway 72 (SC 72) is a 124.860-mile (200.943 km) state highway, traversing interior portions of the South Carolina Piedmont region. This route is part of a multi two-state route 72 that begins at Athens, Georgia and ends at Rock Hill, South Carolina. The route connects many smaller communities outside major metropolitan areas and is roughly parallel with Interstate 85 (I-85) to the north and I-20 and I-77 to the south and east. The route shares the longest concurrency in the state with SC 121, from Whitmire to Rock Hill.
South Carolina Highway 56 (SC 56) is a 63.700-mile (102.515 km) primary state highway in the state of South Carolina. The highway provides a back country alternative to Interstate 26 (I-26) from Clinton to Spartanburg.
South Carolina Highway 10 (SC 10) is a 22.790-mile (36.677 km) state highway in the U.S. state of South Carolina that travels from SC 28 near McCormick to the U.S. Route 25 Business, US 178 Bus., and SC 34 in Greenwood. The highway is a two-lane highway that serves as a connector between McCormick and Greenwood. The first 21.2 miles (34.1 km) is known as McCormick Highway, while the remaining 1.5 miles (2.4 km) is known as Maxwell Avenue.
South Carolina Highway 215 (SC 215) is a 96.330-mile (155.028 km) primary state highway in the U.S. state of South Carolina. It serves as an alternate route to Union from either Columbia or Spartanburg.
South Carolina Highway 92 (SC 92) is a 16.460-mile-long (26.490 km) state highway in the U.S. state of South Carolina. The highway connects Gray Court with the Enoree area.
South Carolina Highway 292 (SC 292) is a 13.640-mile-long (21.951 km) state highway in the U.S. state of South Carolina. The highway connects Duncan and the Inman area, via Lyman.
South Carolina Highway 81 (SC 81) is a 80.890-mile-long (130.180 km) state highway in the U.S. state of South Carolina. The highway connects rural areas of McCormick County with Greenville, via Calhoun Falls, Iva, Homeland Park, and Anderson.
South Carolina Highway 341 (SC 341) is a 93.870-mile (151.069 km) state highway that travels through the northeastern part of the U.S. state of South Carolina. It travels diagonally from the southeast to northwest from SC 41 and SC 51 in Johnsonville to U.S. Route 521 Business and US 601 Bus. in Kershaw.