U.S. Route 421 Business (Gate City, Virginia)
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| Highway system | |
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| Location: | Wilmington, North Carolina |
| Length: | 1.0 mi (1.6 km) |
| Existed: | 2009–present |
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| Location: | Sanford, North Carolina |
| Length: | 9.9 mi (15.9 km) |
| Existed: | 2015–present |
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| Location: | North Wilkesboro, North Carolina |
| Length: | 6.2 mi (10.0 km) |
| Existed: | 1969–present |
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| Location: | Boone, North Carolina |
| Length: | 4.8 mi (7.7 km) |
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| Location: | Gate City, Virginia |
| Length: | 2.65 mi (4.26 km) |
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| Location: | Wilmington, North Carolina |
| Length: | 2.4 mi (3.9 km) |
| Existed: | 1970–1979 |
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| Location: | Clinton, North Carolina |
| Existed: | 1952–1960 |
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| Location: | Clinton, North Carolina |
| Existed: | 1960–1963 |
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| Location: | North Wilkesboro, North Carolina |
| Length: | 4.3 mi (6.9 km) |
| Existed: | 1957–1969 |
Several special routes of U.S. Route 421 exist. In order from south to north they are as follows.
U.S. Route 421 Truck (US 421 Truck), established on March 2009, is a truck route along Front Street from US 421 (Burnett Boulevard) to the Cape Fear Memorial Bridge.
The entire route is in Wilmington, New Hanover County.
U.S. Route 421 Business (US 421 Bus) is a 9.9-mile (15.9 km) multi-lane business loop along Horner Boulevard, through downtown Sanford. Approved by AASHTO on May 3, 2013, its official establishment is dependent on the completion of the Sanford bypass, which mainline US 421 will be rerouted along, sharing with already established NC 87 Bypass.
The entire route is in Lee County.
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