Independence to Roanoke US 221 enters
Grayson County, Virginia from North Carolina concurrent with
US 21. The U.S. Highways follow two-lane undivided New River Parkway, which crosses the
New River a short distance north of the state line. US 221 and US 21 enter the town of Independence as Independence Avenue, which intersects US 58 (Main Street) in the center of town. US 21 continues north on Independence Avenue toward
Wytheville while US 221 turns east onto Main Street. US 221 and US 58 exit the town as Grayson Parkway, which expands to a four-lane
divided highway just west of its intersection with
SR 274 (Riverside Drive). The U.S. Highways parallel the New River for a short distance before crossing the river at one of its bends. US 221 and US 58 pass to the north of the community of
Baywood before meeting the southern end of
SR 94 (Riverside Drive). East of SR 94, US 221 and US 58 enter the
independent city of Galax. The highway is named Reserve Boulevard until just west of downtown, where the highway becomes an undivided highway named Stuart Drive and intersects
SR 89 (Main Street). US 221 and US 58 pass the southern end of
New River Trail State Park before crossing Chestnut Creek and becoming a five-lane road with a
center left-turn lane. The U.S. Highways become a divided highway before entering
Carroll County, where the highway is known as Carrollton Pike. US 221 and US 58 pass through
Woodlawn before meeting
I-77 at a
diamond interchange. The U.S. Highways enter the town of Hillsville as Stuart Drive, a three-lane road with center turn lane. US 221 and US 58 intersect
US 52 (Main Street) in the center of town before the highways diverge. US 58 continues east along Stuart Drive toward
Martinsville while US 221 heads northeast on Floyd Pike, which meets the southern end of
SR 100 (Sylvatus Smith Highway) just east of the town limits. US 221 continues northeast into Floyd County, through which the highway passes as Floyd Highway. The U.S. Highway passes through
Willis and
Shelors Mill before becoming the Main Street of the
county seat Floyd, where the highway intersects
SR 8 (Locust Street). US 221 crosses the
Little River and passes through
Copper Hill before entering
Roanoke County at Adney Gap. Just north of the county line, the U.S. Highway, now known as Bent Mountain Road, intersects a connector road to the
Blue Ridge Parkway, which parallels the U.S. Highway on the western slope of Bent Mountain. North of the hamlet of Airpoint, US 221 descends the east–west section of Bent Mountain between
Poor Mountain to the west and the spine of the
Blue Ridge Mountains to the east. Once the highway is at the bottom of the mountain, it follows Back Creek into the
Roanoke Valley.
City of Roanoke Once in the valley, US 221 becomes Brambleton Avenue, a five-lane road with center turn lane. The highway passes through the suburb of
Cave Spring, where the highway intersects
SR 419 (Electric Road), before entering the city of Roanoke as a two-lane street. US 221 passes to the north of
Virginia Western Community College before reaching Brandon Avenue, which the highway follows east a short distance before veering north onto Main Street. The U.S. Highway heads north through the
Wasena neighborhood before crossing the
Roanoke River and
Norfolk Southern Railway's
Altavista District. US 221 veers east on Elm Avenue through the
Old Southwest neighborhood to Franklin Road. Southbound US 221 follows Franklin Road to the northeast while northbound US 221 continues on Elm Avenue to Jefferson Street, which carries
SR 116 in both directions. There, US 221 turns north; Elm Avenue continues east as
SR 24. US 221 and SR 116 head north past the
Patrick Henry Hotel to Franklin Road, where the highways turn east. After one block on Franklin Road, the highways turn north onto four-lane Williamson Road, on which they head north along the eastern side of
Downtown Roanoke. US 221 and SR 116 are joined by
US 11 at Campbell Avenue. The three highways expand to a divided highway and cross over Norfolk Southern's
Blue Ridge District rail line between the
Roanoke Shops to the east and the
O. Winston Link Museum and
Hotel Roanoke to the west. US 221, US 11, and SR 116 have a partial interchange with
I-581 and
US 220 east of the
Gainsboro neighborhood; the interchange features ramps from northbound US 221 to northbound I-581 and from southbound I-581 to southbound US 221. The highways pass the
Roanoke Civic Center before intersecting Orange Avenue in the middle of the
Williamson Road neighborhood. Orange Avenue carries US 460 and
U.S. Route 220 Alternate through the intersection, and
U.S. Route 11 Alternate west of the intersection. US 11 continues north on Williamson Road, SR 116 turns west onto Orange Avenue, and US 221 turns east onto Orange Avenue.
Roanoke to Lynchburg US 221, US 460, and US 220 Alternate head east as a six-lane divided highway that passes under Norfolk Southern Railway's
Roanoke District and intersects
SR 115 (Hollins Road). The road reduces to four lanes at Tinker Creek and becomes named Challenger Avenue on re-entering Roanoke County. US 220 Alternate turns north onto Cloverdale Road in the community of
Bonsack just west of where US 221 and US 460 enter
Botetourt County. The U.S. Highways continue as Blue Ridge Boulevard and meet the Blue Ridge Parkway at an interchange south of the community of
Blue Ridge, where the highways parallel Norfolk Southern's Blue Ridge rail line through
Buford's Gap to enter
Bedford County. US 221 and US 460 continue east as the Lynchburg Salem Turnpike through the village of
Thaxton to the town of Bedford. Just inside the town limits, the two U.S. Highways diverge: US 460 continues along its bypass of Bedford while US 221 and
US 460 Business head toward the downtown area along two-lane Blue Ridge Avenue. At the west edge of downtown, the highways continue on Main Street and intersect
SR 122 Business (Crenshaw Street) at the
Bedford Historic Meetinghouse. At Bridge Street, US 460 Business and southbound
SR 43 continue east on Main Street while US 221, SR 122 Business, and northbound SR 43 turn north onto Bridge Street to cross the Blue Ridge District rail line. North of the railroad, SR 43 splits northwest on Peaks Street toward the
Peaks of Otter. US 221 and SR 122 Business head northeast on Longwood Avenue to the business route's terminus at
SR 122, which heads south on Independence Boulevard toward US 460 and north on a continuation of Longwood Avenue. US 221 continues east on two-lane Forest Road, exiting the Bedford town limits, and then crossing the
Little Otter River and the
Otter River. After passing
Goode, the U.S. Highway heads through
Forest, the site of
Saint Stephen's Episcopal Church and its
Old Rectory and
Thomas Jefferson's private retreat,
Poplar Forest. At Forest, US 221 enters the suburban area surrounding Lynchburg and enters the independent city itself just west of its intersection with
US 501 (Lynchburg Expressway). The U.S. Highway follows Lakeside Drive east past
Lynchburg College to Oakley Avenue, onto which the U.S. Highway turns to pass through Lynchburg's West End. US 221 intersects
SR 163 (Memorial Avenue) and joins US 460 Business on Fort Avenue next to
Calvin Falwell Field. At Thurman Avenue, the two highways veer onto 12th Street and are joined by a second business route, US 501 Business, at Campbell Avenue. US 221, US 460 Business, and US 501 Business cross over Norfolk Southern's
Danville District rail line and turn southeast onto Kemper Street a few blocks south of
Lynchburg-Kemper Street Station, which is served by
Amtrak. The three highways pass the
Anne Spencer House before US 221 reaches its northern terminus at a
cloverleaf interchange with US 29 Business (Lynchburg Expressway). Kemper Street continues southeast as US 460 Business and US 501 Business toward their termini at
US 29, US 460, and US 501. ==Major intersections==