State Route 821 (SR 821) is a north–south state highway in the southeastern portion of the U.S. state of Ohio. A state-maintained section of the old US 21, its southern terminus is at SR 60 approximately 2 miles (3.2 km) north of Marietta, and its northern terminus is at I-77 in Byesville, along with the eastern terminus of SR 209. The route is entirely undivided surface road, and is much less direct than the newer I-77 which supplanted it as a through route. As the interstate was being built, the designation of US 21 was moved to the freeway before Ohio wholly decommissioned the now-superfluous U.S. route. SR 821 was designated about two years after US 21 was moved onto I-77 in southeastern Ohio.

U.S. Route 21 or U.S. Highway 21 (US 21) is a major north–south United States Numbered Highway in the Southeastern United States that extends 394 miles (634 km). The southern terminus is in Hunting Island State Park, South Carolina, 14.4 miles (23.2 km) south of the junction with US 21 Business and South Carolina Highway 802 (SC 802) in Beaufort. The northern terminus is in Wytheville, Virginia, at an interchange with Interstate 81 (I-81) and US 52. Despite the "1" indicating that it is a major north–south highway, US 21 only travels through three states and is no longer a cross-country route as it has been replaced with I-77 in both Ohio and West Virginia. It also has the second-shortest length of all of the major north–south routes, just behind US 91. The route travels through the states of South Carolina, North Carolina, and Virginia. It also connects through major Southeastern cities such as Columbia, South Carolina, and Charlotte, North Carolina. The northern portion of the road travels parallel to I-77 in northern South Carolina and North Carolina. The road also has three interchanges with I-26 in Lexington and Calhoun counties in South Carolina.