The route follows the western boundary of Lexington's corporate limits, acting as a bypass of the city.

Approved by the American Association of State Highway and Transportation Officials (AASHTO) in September 2005, after receiving an earlier approval from the Federal Highway Administration (FHWA) in July 2005, intending to provide an Interstate-quality freeway to connect Winston-Salem to Charlotte (via a portion of I-85).

The North Carolina Department of Transportation (NCDOT) installed "Future Interstate 285 Corridor" signs along the route in February 2006.

The initial $2.5-million (equivalent to $3.34 million in 2023[3]) project to improve the roadway to Interstate standards was approved in October 2011.

Construction began in March 2014 and included reconstructing shoulders, improving drainage systems, resurfacing travel lanes, and realigning Marco Boulevard to accommodate a new southbound exit ramp alignment at Green Needles Road.

The justification for the 11.3-mile (18.2 km) extension was that Winston-Salem was a major transfer point for motor freight services and that numerous freight operators were already utilizing US 52 to access other major highways in and around the city; and that it would also serve the 330-acre (130 ha) Innovation Quarter, which will house research, business, and several college education facilities.

The transition from future designation is dependent upon completion of the I-74/I-274 interchange and upgrades to interstate standards along the route.