U.S. Route 19 in North Carolina traverses approximately 189 miles (304 km) across Western North Carolina; from the Georgia state line, at the community of Bellview, to the Tennessee state line, at the town of Elk Park. The designation from US 19 to U.S. Route 19E happens in Cane River, where US 19W splits from the main road towards Erwin, Tennessee.

US 19 begins at the Georgia state line overlapped with US 129; 4 miles (6.4 km) into North Carolina, it joins with US 74 and US 76 in Ranger. From Ranger to Andrews, the highway is a 4-lane expressway that bypasses all the towns and communities along its route. After Andrews, US 19 goes through the Nantahala Gorge, which both scenic and somewhat curvy 21 miles (34 km) drive till Almond.

At the start of the Great Smoky Mountains Expressway, US 19 exits off towards the towns of Bryson City and Cherokee. At Cherokee, travelers may go north on US 441 to the Great Smoky Mountains National Park or to the Blue Ridge Parkway before traveling through the rest of the Qualla Boundary.

The highway expands back into a 4-lane expressway in Maggie Valley, which it then merges with the Great Smoky Mountains Expressway for 3 miles (4.8 km) before exiting back off towards Clyde. From here, US 19 parallels with I-40 to Asheville. US 19 joins other highways in Asheville crossing over the French Broad River, then follows I-26 to Mars Hill, North Carolina. At exit 9, US 19 splits with both I-26 and US 23; after 10 miles (16 km), US 19 splits into US 19E and US 19W at Cane River. US 19 travels a total of 145 miles (233 km) from the Georgia state line to Cane River.

US 19E (aka US 19 East) continues where US 19 left off, with a seamless transition that literately ignores US 19W existence, heading towards the towns of Burnsville and Spruce Pine. The highway is an easy drive, as it nears Spruce Pine, it expands to a four-lane that then bypasses the mountain city. US 19E reverts back to two-lane once out of city limits, briefly widening to four-lane again after entering Avery county. Once reaching the community of Ingalls, the highway becomes curvy as it follows along the banks of the North Toe River. Most travelers will take turn onto NC 194 (or Mullen Hill Road, a shortcut bypassing Ingalls) as an alternate route towards Elk Park. Passing through several small communities, it eventually reaches the town of Elk Park, where it then proceeds going into Tennessee, towards Roan Mountain and Elizabethton. US 19E travels a total of 45 miles (72 km) from Bald Creek to the Tennessee state line.

Though the highway is commonly known as "US 19" or "US 19E" throughout the state, the highway does have other known names posted to honor various important citizens.

US 19 is part of two scenic byways in the state (indicated by a Scenic Byways sign).

Nantahala Byway is an 43-mile (69 km) byway from Marble to Whittier; it traverses along the Nantahala River and Tuckasegee River. US 19 overlaps almost the entire route, except south and east of Bryson City. This byway also connects to the Indian Lakes Scenic Byway (at Topton and Almond via US 129 and NC 28).

Mount Mitchell Scenic Drive is an 52-mile (84 km) byway from Interstate 26, through Burnsville, to the summit of Mount Mitchell State Park. It is known for its vistas in and around the Black Mountains. US 19 overlaps from Interstate 26 to Micaville.

Established in 1927, US 19 traversed from the Georgia state line (at Bellview) to the Tennessee state line (at Elk Park), roughly similar to the route seen today. In 1930, US 19 was truncated at Cane River, where it was split into 19E and US 19W; 19E follows the original US 19 routing north. In 1932, it was rerouted in Asheville from Haywood Road to Clingman Avenue, to Hilliard Avenue to Biltmore AVenue towards Broadway Street. In 1937, US 19 was rerouted south of Almond to its current alignment today; while it was rerouted through downtown Asheville again: from Haywood Road to Clingman Avenue to Patton Avenue to College Avenue to Biltmore Avenue towards Broadway Street.

In 1947, US 19 was rerouted from Ela, traversing through Dillsboro, Sylva, and Waynesville, to Lake Junaluska. The old route, through Cherokee and Maggie Valley became US 19A. In 1948, it was switched, having US 19 back along the original route and US 19A going south to Lake Junaluska.

In 1949, US 19 was moved onto the Smokey Park Highway/Patton Avenue as a bypass in West Asheville. The old alignment became US 19A (today's US 19 Business). In 1952, US 19 was rerouted off Martins Creek Road and onto Blairsville Highway, near Ranger. In 1954, US 19 was realigned to its current route from Lake Junaluska to Clyde and Canton; .5 miles (0.80 km) of the old route was replaced by NC 209. Between 1955-57, US 19 was split onto one-way streets in downtown Asheville: Northbound used Patton, to Market, to Woodfin, to Broadway; southbound used Broadway to College, to Patton. In 1961, US 19 removed from downtown Asheville and put on the East-West Expressway, north at Marrimon Avenue. Between 1963-68, US 19 was split onto one-way streets in downtown Canton (Park Street and Main Street). In 1961, US 19 was moved onto new freeway west of Weaverville; the old route became US 19 Business.

In 1973, US 19 was removed from Marrimon Avenue to its current alignment north of Asheville. In 1975, the freeway, US 19 traversed, was extended from Weaverville to Mars Hill. In 1979, US 19 bypassed Andrews, US 19 Business replaced old route. In 1980, US 19 bypassed Murphy, US 19 Business replaced old route. In 1984, US 19 was realigned in Yancey County to its current routing, US 19W was extended .4 miles (0.64 km) south.

On November 2, 2012, US 19/US 19E was widen from Interstate 26 to Jacks Creek Road, just west of Burnsville. At $107.9 million, the 13.6 miles (21.9 km) two-lane mountain road was upgraded to a four-lane highway, and the first for Yancey County. Governor Bev Perdue was on hand at the ribbon cutting ceremony opening the highway.

US 19/74, from Andrews to Almond, is to be realigned onto a new multi-lane highway west of the Nantahala Gorge. The project is broken into several sections, all subject to reprioritization.

US 19/23, from Canton to Candler, is to be widen to a multi-lane highway and its bridge replaced over the Pigeon River. This project is currently funded.

US 19, in concurrency with Interstate 26 and US 23, is planned to be realigned onto a new interchange at Interstate 240 and freeway improvements north from it. Right-of-way purchases is to begin in 2023, however project is unfunded.

US 19/19E, from Interstate 26 to Ingalls, is to be widen into a multi-lane highway. Several sections already exist or completed, with construction currently between Jack Creek Road (west of Burnsville) to Micaville scheduled to complete in 2015. The two remaining sections east and west of Spruce Pine is currently subject to reprioritization.