US Highways Route - US21
| Route | From | To | Miles | States passed through | Replaced by | Notes |
| US 21 | (Cleveland, OH) Wytheville, VA | Hunting Island SP, SC | 393 (843) | (OH) (WV) VA NC SC | OH-21 I-77 OH-21 I-77 OH-259 I-77 OH-821 I-77 US 60 WV-16 WV-61 WV-210 US 19 US 52 I-77 SC-72 US 321 | Since 1926; S exten Beaufort, SC 1935; Curr 1953; N trunc Pocatalico, WV 1971; Curr 1978 |
| (US 121) [I] | (Max Meadows, VA +) | (Lexington, NC) | (107) | (VA) (NC) | US 52 | Exist 1926-1934 |
| |US 121 [II]| | |Beckley, WV| | |Pound, VA| | |132| | |WV| |VA| | Nill | Approved 2005; Estimated open 2007 |
| US 221 | Lynchburg, VA | Perry, FL | 734 | VA NC SC GA FL | NC-194 Alt US 221 | Since 1930; Orig rte Twin Oaks, NC - Ingalls, NC; N extend Roanoke, VA 1932; Curr 1972; S exten Greenwood, SC 1932; Curr 1954 |
| US 321 | Eaton Crossroad, TN + | Hardeeville, SC | 526 | TN NC SC | Alt US 321 NC-155 NC-16 | Since 1930; Orig rte Bristol, TN - Chester, SC; S exten 1949; N exten Johnson City, TN 1961; Curr 1981 |
| US 421 | Michigan City, IN | Ft. Fisher, NC | 941 (980) | IN KY VA TN NC | KY-55 KY-22 US 58 US 25E NC-133 US 117 | Since 1930; Orig rte Boone, NC - Greensboro, NC; S exten Wilmington, NC 1931; N exten Cumberland Gap, VA 1933; N trunc Bristol, TN 1934; N re-exten Cumberland Gap, VA 1935; N exten Bedford, KY 1950; N curr 1951; S exten 1935 |
| US 521 | Charlotte, NC | Georgetown, SC | 191 | NC SC | SC-261 SC-261 SC-377 | Since 1933; Orig begin Pineville, NC |
| US 23 | Mackinaw City, MI | Jacksonville, FL | 1444 (1476) | MI OH KY VA TN NC GA FL | MI-68 MI-33 OH-51 OH-65 OH-199 OH-423 US 123 [I] US 119 | Since 1926; S exten Middlesboro, KY 1929; S trunc Jenkins, KY 1930; S exten Lawrenceville, GA 1930; Atlanta, GA 1932; Curr 1950 |
| (US 123) [I] | (Jenkins, KY) | (Middlesboro, KY) | (96) | (KY) | US 119 US 25E | Exist 1930-1934; Was US 23 |
| US 123 [II] | Greenville, SC | Baldwin, GA | 87 | SC GA | Nill | Since 1937 |
| US 223 | Somerset, MI | Sylvania, OH (Toledo, OH) | 48 (56) | MI OH | OH-51 | Since 1930; S trunc 1987 |
| US 25 | (Port Austin, MI) Covington, KY - | Brunswick, GA | 750 (1151) | (MI) (OH) KY TN NC SC GA | MI-25 MI-3 I-94 I-75 US 24 MI-125 US 24 OH-25 I-75 US 42 US 25W NC-225 US 80 | Since 1926; /E//W//E//W/ S exten Savannah, GA 1930; S trunc Statesboro, GA 1932; S exten 1935; N trunc 1974 at OH-KY border |
| US 425 | Pine Bluff, AR | Natchez, MS | 108 | AR LA MS | Nill | Since 1989; IMO this should be US 265; Since 1989; Never connected to US 25; N exten 2002; S exten 2005 (signed 2006 to Vidalia, LA) |
| US 27 | (St. Ignace, MI) Ft. Wayne, IN | Miami, FL | 1364 (1749) | (MI) IN OH KY TN GA FL | US 127 I-69 MI-27 I-75 IN-127 | Since 1926; S exten Chattanooga, TN 1928; Tallahasssee, FL 1934; Curr S exten 1949; N trunc Grayling, MI 1962; N trunc Lansing, MI official 1999; Curr N trunc official in 2000; Signs changed 2002 |
| US 127 | Grayling, MI | Chattanooga, TN | 758 | MI OH KY TN | US 223 OH-51 | Since 1926; S trunc Somerset, MI 1930; S exten Cincinnati, OH 1930; Curr 1958; Curr N exten official 2000; Signs changed 2002 |
| (US 227) | (Carrollton, KY) | (Richmond, KY) | (120) | (KY) | KY-227 US 460 KY-627 KY-338 | Exist 1928-1972; Orig begin Paris, KY; N exten 1930 |
| US 29 | (Baltimore, MD) Mount Hebron, MD | Pensacola, FL | 1036 (1060) | MD DC VA NC SC GA AL FL | US 40 MD-144 FL-95A | Since 1926; N exten Culpepper, VA 1932; Baltimore, MD 1934; N trunc 1949; S exten 1935 |
| US 129 | (Corbin, KY) Knoxville, TN | Chiefland, FL | 582 (682) | (KY) TN NC GA FL | US 25W Alt US 129 Alt US 129 FL-349 | Since 1926; N exten AASHTO 1935-1952; N trunc KY-TN 1936; S exten 1948 |
U.S. Highways
| US 1 | US 11 | US 21 | US 31 | US 41 |
| US 51 | US 61 | US 71 | US 81 | US 91 |
| US 2[I] | US 10 [I] | US 20 [I] | US 30 | US 40 |
| US 50 | US 60 | US 70 | US 80 | US 90 |