U.S. Route 21 in South Carolina
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| Length: | 394 mi (634 km) | |||||||||
| Existed: | 1926 – present | |||||||||
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| South end: | Hunting Island State Park, SC | |||||||||
 I-95 near Yemassee, SC I-26 (three times in SC) I-20 in Columbia, SC I‑77 (numerous times in SC/NC) I‑85 in Charlotte, NC I‑40 in Statesville, NC
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| North end: |
  I‑81 / US 52 in Wytheville, VA
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| States: | South Carolina, North Carolina, Virginia | |||||||||
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U.S. Route 21 (US 21) is a north–south United States Numbered Highway that runs 394 miles (634 km) from Hunting Island State Park, South Carolina to Wytheville, Virginia.
US 21 travels 233.2 miles (375.3 km) through the state. Beginning at Hunting Island State Park, US 21 travels west toward Beaufort, where it widens to four lanes. The route bypasses Beaufort to the south, going through Port Royal, Shell Point, and Burton. In the Beaufort area, US 21 passes by the entrances to Parris Island and MCAS Beaufort, the major Marine Corps installations in the area. North of Beaufort, US 21 continues as a four-lane divided highway and intersects with US 17. The route travels in a wrong-way concurrency with US 17 south for seven miles (11 km) before turning north towards Yemassee, South Carolina, where it becomes a rural two-lane road and intersects with US 17 Alternate. North of Yemassee, US 21 splits off and crosses Interstate 95 (I-95) at exit 42.
The two-lane route continues through rural portions of the state. US 21 goes through Smoaks and Branchville, South Carolina and bypasses Orangeburg. North of Orangeburg, US 21 runs roughly parallel to I-26 until Gaston where it conjoins US 321 and becomes an urban highway. US 21 passes through Cayce, West Columbia, and Columbia (passing by the State House).
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