U.S. Route 25 is a north–south United States highway that runs for 75.4 miles (121.3 km) from the South Carolina state line, near Tuxedo, to the Tennessee state line, near Hot Springs.

From the South Carolina state line, US 25 becomes a freeway for 9 miles (14 km) before connecting with I-26/US 74 near Flat Rock (section between exits 5-9 are currently being upgraded to freeway grade, to be completed in 2012). Splitting onto 4-lane road from I-26/US 74, it goes north through Fletcher to Arden where it US 25A diverges from the mainline to the east along Sweeten Creek Road. Continuing, US 25 goes through Skyland and Biltmore Forest before entering the Asheville near I-40. The immediate area after the interstate is known as Biltmore Village, where US 25A merges back and the Biltmore Estate is located. Passing over the Swannanoa River, US 25 enters the downtown area along McDowell Street then onto Southside Avenue and Biltmore Avenue. US 25 goes through the center of Asheville, which is marked by on Obelisk to Zebulon Baird Vance. From the city center, it continues on Broadway Street to I-240, where it switches onto Merrimon Avenue to leave Asheville. The road drops from 4-lane to 2-lane at Beaver Lake for 1.7 miles (2.7 km) before connecting with I-26 again near Woodfin. At Weaverville, US 25 and US 70 leave together, going northwesterly to Marshall along 4-lane highway. Immediately after passing Marshall, the highway drops down to 2-lane as it continues west, through Hot Springs, to Tennessee.

US 25 is part of two scenic byways in the state (indicated by a Scenic Byways sign).

French Broad Overview is an 17-mile (27 km) byway from Weaverville to Marshall; it is known for its scenic views along the French Broad River. The byway begins at the Monticello Road intersection in Weaverville, where it connects with NC 251 along the banks of the French Broad River; it continues north, switching to US 25/70 Business into Marshall and it back along US 25/70.

Appalachian Medley is an 45-mile (72 km) byway from near Lake Junaluska to Walnut; it is known for several recreational areas, the Appalachian Trail, and its scenic mountain drive. US 25/70 is on 10 miles (16 km) of the byway from Walnut to Hot Springs, where it continues via NC 209.

Established as an original U.S. Route (1926), US 25 followed NC 29 from South Carolina, through Tuxedo, Flat Rock, Hendersonville, and Biltmore Forest, to Asheville. In the downtown area, US 25 links-up with U.S. Route 70 in North Carolina/NC 20 on College Street; it then proceeds north along Merrimon Avenue out of the city. Following Old Marshall Highway to Marshall, it continues along the same route as today into Tennessee. In 1929, NC 29 was replaced by an extension of NC 69; in 1934, both NC 20 and NC 69 were dropped from the route.

Around 1933, US 25 was rerouted along McDowell Street from Biltmore Avenue. During the mid-1950s, US 25 was split onto one-way streets in Hendersonville (northbound King Street/southbound Main Street); by the early 1960s, southbound traffic moved onto College Street, replacing US 25 Alternate (originally established sometime in 1939-1944 as a bypass through the main roads of town).

In 1960, a bypass north around Marshall was completed, old route through town became US 25 Business (along with US 70). Around 1969, the community of Walnut was bypassed. In 1981, US 25 was moved onto the existing US 19/US 23 freeway north of Asheville, it then went onto new 4-lane road west of Weaverville; the most of the old route was replaced by NC 251.

In 1974, US 25 was placed onto new expressway between Zirconia to the South Carolina state line, the old route would later become part of NC 225 in 1998. In September, 2003, US 25 was rerouted onto I-26/US 74, bypassing Flat Rock and Hendersonville, then replacing part of NC 225 that bridged the connection from the interstate to Zirconia. The old route was replaced by NC 225 through Flat Rock and US 25 Business through Hendersonville via US 176.

Currently, there is one U.S. Route 25 Alternate route in North Carolina:

Historically, another US 25 Alternate route existed in Hendersonville (between 1939-42 till 1958-62); it was signed along Church Street until it was converted to one-way streets, becoming US 25 southbound. Today, it is part of US 25 Business.

Currently, there are two U.S. Route 25 Business loops in North Carolina: