Interstate 40 (I-40) is a part of the Interstate Highway System that travels from Barstow, California, to Wilmington, North Carolina. In North Carolina, I-40 travels across the entirety of the state from the Tennessee state line along the Pigeon River Gorge to U.S. Highway 117 (US 117) and North Carolina Highway 132 (NC 132) in Wilmington. I-40 is the longest Interstate Highway in North Carolina and is the only Interstate to completely span the state from west to east.

Traveling from west to east, I-40 connects the three major regions of North Carolina—Western North Carolina, the Piedmont, and Eastern North Carolina. In the Piedmont region, I-40 connects the Piedmont Triad and Research Triangle metropolitan regions. Included in these regions are the cities of Raleigh, Greensboro, Durham, and Winston-Salem, which represent the second through fifth largest cities in the state, respectively. In addition, I-40 connects the cities of Asheville and Hickory in Western North Carolina, Wilmington in Eastern North Carolina, and many smaller communities along its route. The landscapes traversed by I-40 include the Blue Ridge Mountains, the foothills of Western North Carolina, suburban communities, the urban core of Piedmont cities, along with Eastern North Carolina farmland. There are five Interstate auxiliary routes of I-40: I-140, I-240, I-440, I-540, and I-840.

The freeway bears several names in addition to the I-40 designation. Throughout the state, the freeway is known as the Blue Star Memorial Highway, a name shared with multiple Interstates across the state. From the Guilford–Alamance county line to east of NC 54, in Graham, I-40 and I-85 is known as the Sam Hunt Freeway. From Orange County to Raleigh, I-40 is known as the Harriet Morehead Berry Freeway, John Motley Morehead III Freeway, Dan K. Moore Freeway, and Tom Bradshaw Freeway. I-40 is the James Harrington Freeway from US 70 to I-95. In Duplin County, a section of I-40 is known as the Henry L. Stevens Jr. Highway. From the Pender–New Hanover county line to the eastern terminus of I-40, the freeway is known as the Michael Jordan Highway.

I-40 was an original Interstate Highway planned in the Federal-Aid Highway Act of 1956. In North Carolina, the original highway was to run from the Tennessee state line to Greensboro, where the freeway would end at I-85. In 1958, the first section of completed Interstate Highway in the state was I-40 along the East–West Expressway in Winston-Salem. I-40 received two extension approvals; the first in 1969 to I-95, to be routed in or near Smithfield, and the second in 1984 to Wilmington. The last section completed was the Winston-Salem rerouting in 1992. The highest point is at , located at the Swannanoa Gap, and the lowest point is at , located at the Pender–New Hanover county line.

Route description I-40 travels through all of the diverse regions characteristic of the geographies in North Carolina. Annual average daily traffic counts along the Interstate in 2023 reached a peak of 193,099 vehicles per day from Harrison Avenue (exit 287) to Wade Avenue in Raleigh. The lowest count was a total of 21,288 vehicles per day in a rural stretch of Pender County. All of I-40 is part of the National Highway System, a network of roads important to the country's economy, defense, and mobility. I-40 is also designated as a Blue Star Memorial Highway throughout the state.

Western North Carolina

I-40 enters North Carolina along the north banks of the Pigeon River at the foot of Snowbird Mountain. Winding in parallel with the river, I-40 goes through twin tunnels. When the tunnels opened in 1968, they were the first Interstate tunnels east of the Mississippi River. I-40 then proceeds through the Pigeon River Gorge for the next . Just south of exit 7, I-40 uses another tunnel, for eastbound traffic only, through Hurricane Mountain. The westbound lanes use a rock cut through Hurricane Mountain. A short distance after the tunnel is the North Carolina Welcome Center. Immediately afterward is Waterville Lake, where there are a few at-grade intersections in this location, used as service access for Walters Dam and the Harmon Den Wildlife Management Area. I-40 continues toward Asheville. The Interstate then merges with US 74 (Great Smoky Mountains Expressway). I-40 and US 74 encounter the I-26/I-240 interchange, sometimes called Malfunction Junction, in the southwestern part of the city. The interchange is the current western terminus of I-240 and the original western terminus of I-26. I-40 then goes along the south side of Asheville, north of the Biltmore Estate toward Hickory. I-40 then has another interchange with I-240 before the Interstate leaves the Asheville area.

Shortly after it leaves Asheville, I-40 encounters a steep grade, Old Fort Mountain, with winding roads that pose a hazard to truck traffic. There are several runaway truck ramps on this part of the highway. This stretch is about long. I-40 goes south of Black Mountain and Marion and north of Conover. There, it crosses the Eastern Continental Divide and the southern tip of the Black Mountains. The Interstate enters into Hickory, where it comes to a cloverleaf junction with US 321 (with collector-distributor lanes included). This gives northern access to central Hickory and southern access to Lincolnton and Gastonia.

Piedmont region

The Interstate crosses the Catawba River, on the Cecil H. Hoffman Bridge, upon entering into the northern outskirts of the Metrolina region, where it enters into Iredell County. In Statesville, I-40 comes to the junctions with US 64 and US 21, before widening to six-lanes. The Interstate comes to the partial turbine/cloverleaf interchange with I-77, with additional collector lanes. I-40 continues northeast, while exiting Statesville and becoming four lanes, where it enters the southwestern outskirts of the Piedmont Triad. The Interstate traverses Mocksville and the surrounding forestry areas, including the areas that surround Farmington. I-40 then widens to generally six lanes, where it comes to the exit with NC 801, which is inside Bermuda Run. It is also in this vicinity, where I-40 crosses the Yadkin River, which serves in being the transition between eastern Davie County and western Forsyth County. I-40 traverses the Village of Clemmons, upon coming to the Winston-Salem city limits. Eastbound I-40 has access to Downtown Winston-Salem and the surrounding areas via the four-level stack/cloverleaf interchange with US 421 and Salem Parkway, which gives the left-exit orientation for the eastbound access. US 421 gives eastbound entrance and westbound exit in its connection with I-40, with Salem Parkway also being accessible from westbound I-40. I-40 gradually rotates to an east-west orientation, where the westbound and eastbound lanes are separated; with Westbound I-40 being two-three lanes while crossing over the Salem Parkway ramps, while Eastbound I-40 is mostly two lanes. The separate lanes adjoin before coming to the Stratford Road (US 158) exit. I-40 travels south of the parking site of Hanes Mall, with the Stratford Road (US 158) exit giving east–west access to the mall, while the junction with Hanes Mall Boulevard gives westbound access, and both exits also give access to Forsyth Medical Center (direct signage to Hanes Mall is mostly not present). The Interstate is eight to ten lanes in the vicinity of the Hanes Mall Boulevard exit, when merging lanes are included.

I-40 returns to six overall lanes while traversing inside the southern outskirts of the overall downtown area, in which the trumpet interchange with Peters Creek Parkway (NC 150), gives access to the district of downtown and the surrounding areas. This occurs before I-40 comes to the cloverleaf interchange with I-285/US 52/NC 8; in which, US 52/NC 8 gives access to the city of Mt. Airy; while I-285, in concurrency with US 52/NC 8, gives access to the city of Lexington. I-40 comes to a trumpet interchange, with ramps that continue along NC 192 (which connects to Ridgewood Road), occurring before I-40 briefly becomes four lanes. The Interstate soon widens to overall six-eight lanes, when coming to the stack/cloverleaf interchange with the Winston-Salem Northern Beltway (I-74) (I-40 Exit 198), in which this junction connects to High Point and Wytheville, alongside giving Westbound I-40 direct access to Downtown Winston-Salem, and Eastbound I-40 access to central Kernersville. I-40 enters the Town of Kernersville upon crossing the junction with I-74, where I-40 becomes four lanes after it continues to travel inside the town.

The Interstate, when traveling east of the NC 66 junction, enters the surrounding rural landscapes while entering Guilford County. I-40 enters into the transitional vicinity which surrounds Colfax, where it comes to the Salem Parkway (US 421) half-interchange, in which US 421 merges onto I-40, alongside the interchange giving Westbound I-40 access to Downtown Kernersville. I-40 widens to eight overall lanes, in which, the corridor comes to the diamond interchange with Sandy Ridge Road, which gives access to the overall areas of Colfax. The Interstate enters Greensboro, where it comes to the interchange with NC 68, which gives access to the nearby PTI Airport and High Point. The corridor briefly widens to twelve lanes when coming to the I-73/I-840 (Greensboro Urban Loop) multi-level interchange, which is the east end of the US 421 concurrency with I-40, alongside the western terminus of I-840. In the vicinity, I-40 continues alongside the right lanes, where it crosses over the junction with six-to-eight overall lanes. I-40 comes to the folded diamond interchange with Guilford College Road, which gives access to the namesake college and Jamestown, before coming to the parclo interchange with US 70 (Wendover Avenue).

The Interstate continues inside the south-central areas of the city, while also entering the Four Seasons Town Centre and Greensboro Complex district. The junction with Gate City Boulevard gives east–west access to the Mall and the Complex, while Koury Boulevard gives access to Four Seasons Town Centre and the Koury Convention Center westbound. This happens before having the coming a mostly-cloverleaf interchange with US 220 (Freeman Mill Road), which gives access to the Greensboro Complex. US 29 merges onto I-40/US 220, in which the three routes travels concurrently, for over after the interchange with US 220. The junction with US 29 is the mediator between I-40, and the access points to High Point and Charlotte. I-40 continues east, with the interchange with Elm-Eugene Street giving access to the center of downtown and to the surrounding areas. This occurs before the Interstate comes to the US 29/US 220/Martin Luther King Jr. Boulevard junction, which is the end of the concurrent routes. I-40 comes to the junction with East Gate City Boulevard and Lee Street, which gives Westbound I-40 access to Downtown Greensboro and the surrounding areas, before I-40 comes to a combined interchange with the Greensboro Urban Loop, which also gives east-west access with I-85, alongside the junction also being the interchange with I-785 and the eastern terminus with I-840. I-40 merges onto I-85, where the combined junctions also connect with an interchange with Mt. Hope Church Road, which connects to the areas inside McLeansville. I-85 and I-40 share the concurrency while exiting Guilford County, and entering into Alamance and Orange counties. This concurrency section uses the exit and mileage numbers of I-85, while traversing south of the downtown centers of Elon, Burlington, Graham, Mebane, and the surrounding areas. I-85 and I-40 also traverse through the Piedmont Crescent.