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The Salem Parkway is an 18.5 mile (30 km) freeway in the U. S. state of North Carolina, serving the city of Winston Salem and the town of Kernersville. It is signed as U. S. Route 421 (US 421) for its entire length, though it is also concurrent with US 158 in downtown Winston Salem and North Carolina Highway 150 (NC 150) between Winston Salem and Kernersville. Originally known as the East–West Expressway, it was designated as part of Interstate 40 (I 40) and opened in 1958, becoming the first section of Interstate Highway in the state. I 40 was rerouted onto a new alignment bypassing Winston Salem and Kernersville in 1992, at which time the road was designated Interstate 40 Business, nicknamed Business 40. Beginning in November 2018, a 1.2 mile (2 km) section of the freeway in downtown Winston Salem between Peters Creek Parkway (NC 150) and the John Gold Memorial Expressway (US 52) was closed for reconstruction to rebuild the substandard roadway, exit and entrance ramps, and bridges. The section east of Main Street reopened August 30, 2019. though signage outside of the project area had been changed in late December 2019.

In 1954, Winston Salem gave the state $1 million to buy right of way for what was called the East–West Expressway; construction began that same year. Though it was planned to become a new routing of US 158, that changed two years later, when the Federal Aid Highway Act of 1956 was passed and North Carolina was allocated 714 mile (1149 km) for their share of the Interstate Highway System; 219 mile (352 km) was subsequently allocated for a route from the Tennessee state line, through Asheville and Winston Salem, to Greensboro. With the designation of I 40, the East–West Expressway would become the first completed section of Interstate in the state. On January 6, 1958, the first 1.2 mile (2 km) section of the East–West Expressway was opened between Cloverdale Avenue and Main Street. Because of the novelty, local newspapers ran a series of stories and diagrams on how to use the expressway, educating the public on how on ramps and off ramps work. In 1960, the expressway was extended west into Yadkin County, at NC 801, and east to Reidsville Road. In 1961, US 421 was rerouted from Pfafftown and downtown Winston Salem onto new freeway that connected directly with the expressway, then continued easterly running concurrently with I 40. In 1962, US 158 was realigned to continue along the expressway to Reidsville Road, its former alignment became US 158 Business (decommissioned in 1970). East of Reidsville Road, I 40/US 421 was extended onto new freeway to Kernersville, where it then linked with second built section of I 40 (late 1958) and continued towards Greensboro.

Since its opening in 1960, the Hawthorne Curve, a 10° S curve overpass of Hawthorne Road, became an infamous accident prone location; typically speed related, cars and trucks wrecking against the curve and in some cases jumping the guard rail and falling 35 feet (11 m) off the overpass. Blame for the curve mostly fell on then Winston Salem Mayor Marshall Kurfees, who is believed to have ordered the curve to protect political allies who owned businesses on Hawthorne Road and First Street. Kurfees spent the rest of his life denying the allegation, stating that the engineers designed it while he had no input to the project. Over the years, several studies were done and various little fixes were made to improve the situation including a reduced speed zone, better guardrails and the installation of blinking lights and flashing warning signs. In January 1998, the first major improvement in 40 years started with the realignment of Hawthorne Curve. At a cost of $26 million, construction lasted for two years building a new overpass and reshaping the sharp curve to a more gentle one. It was completed seven months early in the middle of 2000.

In February 2008, I 40 was rerouted onto new freeway south of Greensboro, becoming part of the Greensboro Urban Loop. The old route through Greensboro became an extension of I 40 Business, with a 6 mile (10 km) hidden concurrency along I 40/US 421, between exits 206 and 212. This extended the route 20 mile (32 km), ending at a new terminus with I 85/I 40, near McLeansville. However, NCDOT officials received many complaints by local residents and motorists on the confusion between the new I 40 and I 40 Business. Another issue was that funding for construction and repairs on the old route was slashed since it was no longer designated as an Interstate (Interstate business routes are not officially part of the Interstate Highway System) On September 12, 2008, with permission from the FHWA, I 40 was moved back to its old route through Greensboro, decommissioning Business 40 through Greensboro.

Construction began in June 2013 on the first phase of a project to extend Macy Grove Road around the east side of Kernersville. Macy Grove Road, which previously passed over Business 40 with no interchange and ended at Old Greensboro Road, was extended to a temporary terminus at a connector to East Mountain Street, with a diamond interchange built connecting it to Business 40. The extension and interchange opened in May 2015, at which point the former partial interchange with East Mountain Street immediately east of the NC 66/NC 150 interchange was closed and demolished and the westbound roadway through the former interchange realigned closer to the eastbound roadway. In October 2020, NC 150 was rerouted onto Macy Grove Road from the Salem Parkway interchange to the Main Street intersection as Macy Grove Road was extended north from its section built in 2015.

In 2006, the North Carolina Department of Transportation (NCDOT) decided to rebuild the freeway between Fourth Street and Church Street, which covers most of the original 1.2 mile (2 km) section of the East–West Expressway from 1958. For the next ten years, NCDOT made several studies and a series of public meetings before awarding a design build contract with Flatiron Constructors, Inc./Blythe Development Company Joint Venture and HDR Engineering, Inc., in September 2016, to complete the final design and construct the project. Considered as a $100 million do over, the project included: replacing the existing roadway pavement, modernizing entrance and exit ramps, replacing nine vehicular bridges, adding two pedestrian bridges, lengthening the acceleration and deceleration lanes between ramps and widening existing roadway shoulders and adding new ones. When Salem Parkway opens, contractors will still be working on final touches. The opening speed limit will be Once the project is totally completed, the speed may increase to
NCDOT had also decided that once construction was completed, that I 40 Business would be decommissioned and a new name would be given to the freeway alongside the existing US 421 designation. The rationale was the continued confusion locals and travelers have between I 40 and I 40 Business. In November 2015, the residents of Winston Salem metro area were allowed to submit a nomination for a new name, with a January 30, 2016, deadline. A selection committee, which included appointments from Winston Salem and Kernersville, whittled the list to just four for another public vote. The eventual four finalist names were: Golden Leaf Parkway, alluding to the region's tobacco growing and processing heritage; Innovation Highway, showing the high tech aspirations of the area; Piedmont Corridor, identifying geographic location in a highly developed part of the state, and Salem Parkway, which refers to the Moravian settlement founded in 1766. On October 21, 2016, Governor Pat McCrory announced, at the project's ground breaking event, the new name of the freeway as the Salem Parkway; which was the overwhelming favorite, receiving 53% of the vote. This name change took place when the highway reopened on February 2, 2020,

First phase of construction was focused on and around Peters Creek Parkway (NC 150), which included lowering the freeway to establish a minimum vertical clearance of 17 feet (5 m) at the new Fourth Street two lane bridge and 17.5 feet (5 m) at the new seven lane Peters Creek Parkway bridge. After two years of intermittent closures, the new Peters Creek Parkway bridge was opened on November 12, 2018. On November 17, the second phase began with the complete shutdown of Business 40 between Peters Creek Parkway and John Gold Memorial Expressway (US 52/US 311/NC 8); three alternate routes were set up through the downtown area for locals while travelers are encouraged to remain on mainline I 40. During construction, Business 40 was lowered to establish a minimum vertical clearance of 17 feet (5 m) for the new Marshall, Cherry, Main and Church Street bridges; Spruce Street bridge was removed and Liberty Street changed from an underpass to an overpass as a result. The Broad Street interchange was permanently closed and removed, the Cherry Street interchange will be modified with Marshall Street, and the Main Street interchange was modified to have only a southbound on ramp and a northbound off ramp. Two pedestrian bridges will also be completed, one of which will replace Green Street Bridge, and a Strollway Bridge adjacent to Liberty Street. On August 30, 2019, the section east of Main Street was opened. Reconstruction of the downtown segment was completed February 2, 2020.