U.S. Route 52 is a north–south United States highway that runs for 150 miles (240 km) from the South Carolina state line, near McFarlan, to the Virginia state line, near Mount Airy. It serves as a strategic highway through the central North Carolina Piedmont.

US 52 enters North Carolina at Mount Airy. A bypass around Mount Airy, which carries US 52 is designated as the Andy Griffith Parkway. It goes by Pilot Mountain one of the most distinctive natural features in North Carolina. Through the Piedmont Triad region, US 52 is mostly a limited-access freeway. The route joins Interstate 85 Business into Lexington, North Carolina and shares Interstate 85 around Salisbury, North Carolina. The segment of US 52 from Interstate 40 in Winston-Salem, North Carolina to Lexington is currently being upgraded to Interstate highway standards for the future Interstate 285 corridor. The segment from northern Winston-Salem to just south of Mount Airy is expected to form part of the Interstate 74 corridor through North Carolina.

South of the Triad area after splitting from Interstate 85 in Salisbury, US 52 is typically a two-lane route linking some of the state's smaller cities and towns. Albemarle is the largest municipality along this segment of US 52 to the South Carolina state line.

US 52 was established in 1934 as a replacement of US 121/NC 66 from the Virginia state line, near Mount Airy, to Lexington and replacement of US 601/NC 80 from Lexington to the South Carolina state line, near McFarlan.

In the mid-1930s, US 52 was placed on current routing between Rocky River-Norwood and Misenheimer-Gold Hill. In Wadesboro, US 52 was routed along Morgan-Washington-Martin Streets; while in Stokes County, US 52 was placed on new road between Pilot Mountain and King.

In 1941, US 52 was removed from Salisbury Road and placed on its current routing, with US 29/70, south of Lexington. Between 1945-1949, US 52 was split in downtown Winston-Salem: northbound using the original Main Street route, southbound using Liberty Street and First Street. In 1949, US 52 was placed on a new bypass east of Pilot Mountain, leaving US 52A along the main street route.

In 1952, US 52 was placed onto new northern bypass of Lexington, its old route through became part of US 29A/70A and NC 8. In 1953, US 52 was placed onto new western bypass of Mount Airy, its old route through became US 52A (today US 52 Business). In either 1956 or 1957, US 52 was placed on its current route through Wadesboro, via US 74; also around same time period, US 52 was removed from Old Fancy Gap Road near the Virginia state line.

From 1960-1972, the next series of changes were in the Winston-Salem area; starting in 1960 with US 52 was removed from Main Street and onto Old Salem Road. In 1962, US 52 northbound was changed to Main Street, Fifth Street, and Liberty Street. By 1964, US 52 was placed onto new freeway from Winston-Salem, just south of East-West Expressway, to Pilot Mountain; this replaced the old route from Stanleyville to Pilot Mountain, becoming simply Old US 52. By 1973, US 52 was completed moved onto the completed North-South Expressway in Forsyth County, completely removing US 52 from all regular roads through the county.

In 1971, US 52 was joined with I-85, from the Yadkin River to Salisbury, leaving the downtown area. In 1980, the freeway from Forsyth County extended into Davidson County at Midway. By 1982, New London was placed on a short bypass west of town. Between 1985-1987, US 52 was given its current Albemarle bypass routing; in October, 2010, the routing was rebuilt along its southern portion. Between 1991-1993, US 52 was extended further south onto new freeway from Midway to Welcome in north Davidson County; by 1995, the freeway connected with the Lexington bypass, completing US 52's move from rural road to freeway from Lexington to Mount Airy.

Currently there is plans to widen US 52 between Wadesboro to NC 24/NC 27, in Albemarle, to four-lanes by around 2015 (STIP: R-2320).

In the more distant future, US 52 between NC 65, in Winston-Salem, to I-74, near Mount Airy, is planned to be reconstructed to interstate-grade standards (STIP: I-4404).

In Winston-Salem, a bridge replacement (built in 1964) is currently under construction that crosses over Liberty Street and the Norfolk Southern Railroad Switching Yard. The project includes widening of Liberty Street, ramp improvements along US 52, and install new traffic signals in area. It is estimated at $19 million and to be completed on November 1, 2012.

Upgrades of US 52 to interstate grade, between Interstate 85 and Interstate 40/US 311 are estimated to cost $8.725 million. Property acquisition will start in June, 2012, with construction scheduled for May, 2013. Once completed, US 52 will be in concurrency with Interstate 285.

Though the highway is commonly known as "Highway 52" or "U.S. 52" throughout the state, the highway does have other known names it uses locally in areas.

The Andy Griffith Parkway is an 11 mile (18 km) section of U.S. Route 52 in northern Surry County, North Carolina dedicated in honor of actor Andy Griffith. U.S. Route 52 through this stretch is a limited- controlled-access four-lane divided highway. Approximately 5.5 miles (8.9 km) of the 11 mile (18 km) section passes through the corporate limits of Griffith's hometown of Mount Airy, North Carolina.

Due to its close proximity to Pilot Mountain State Park, in 1977 U.S. Route 52 through Surry County and Stokes County was dedicated as the Pilot Mountain Parkway by the North Carolina Department of Transportation. However, in March 2002, the North Carolina Department of Transportation was approached by a grassroots group of residents of Mount Airy that felt that a highway dedication for Griffith was long overdue.

The group proposed to rename an 11 mile (18 km) section of the Pilot Mountain Parkway running from the Interstate 74 interchange north to the Virginia state line to the Andy Griffith Parkway.The Pilot Mountain Parkway designation would remain from the Interstate 74 intersection south through Stokes County.

The group had the support of the dedication from several North Carolina state agency officials that included: Governor Mike Easley, State Treasurer Richard H. Moore and NCDOT Division 11 Board Member Sam Erby. Each of these officials played an integral role in expediting the renaming through the North Carolina Department of Transportation's Road and Bridge Naming Committee. The dedication also had the full support of Andy Griffith. The NCDOT Road and Bridge Naming Committee voted unanimously for the dedication at their July, 2002 meeting in Raleigh, North Carolina.

A dedication ceremony was held on October 16, 2002 in the parking lot behind City Hall in Mount Airy. Andy Griffith accepted the invitation to attend the ceremony. It was Griffith’s first public appearance in his hometown in over 40 years.

Also in attendance were: Griffith’s wife Cindi Griffith, Governor Mike Easley, former University of North Carolina President William C. Friday, Grandfather Mountain developer Hugh Morton, as well as many more State and local officials. More than 3000 Andy Griffith fans also attended to welcome Andy Griffith back to Mount Airy.