Nominally east–west, as indicated by its even number, I-26 runs from the junction of US Route 11W (US 11W) and US 23 in Kingsport, Tennessee, generally southeastward to US 17 in Charleston, South Carolina.

When the extension was made in 2003, the exit numbers in North Carolina were increased by 31 to reflect the new mileage.

After about 1,000 yards (910 m), I-26 crosses the South Fork Holston River before swinging around to a generally southeast path through Sullivan County.

It meets the Nolichucky River just after milemarker 38 and travels along its southeast bank before crossing it immediately before exit 40.

The remainder of I-26 in Tennessee passes through a sparsely populated area, at elevations of above 1,800 feet (550 m), before reaching the North Carolina state line.

Future I-26, which is not signed I-26 because it does not yet meet all interstate standards, then passes through Mars Hill and Weaverville.

After coming into Asheville from the north, I-26 merges with I-240 and the two share the highway for 4.5 miles (7.2 km), crossing French Broad River in the process.

The land flattens substantially after entering the French Broad River drainage basin from Arden, Fletcher, and Hendersonville to Flat Rock in Henderson County.

I-26 heads down a six-percent grade for the next three miles (4.8 km) through Howard Gap, into Polk County, and intersects with US 74, a limited-access freeway near Columbus, at an elevation of around 1,100 feet (340 m).

After I-95, the highway travels southeast over flat plains with little urbanization past Summerville until it reaches its eastern terminus in Charleston.

[citation needed] The first section of I-26 in North Carolina consisted of 14 miles (23 km) of the Interstate near Hendersonville, which opened in January 1967.

[citation needed] The planning for an extension of I-26 from Asheville to I-81 near Kingsport started in 1987 to accommodate truckers traveling toward I-81 that were banned on US 19 and US 23.

In Tennessee, I-181 traversed from US 321/State Route 67 (SR 67), in Johnson City, to US 11W/SR 1, in Kingsport, totaling 23.85 miles (38.38 km).

In 2005, the numerical extension was enacted by the effect of the Safe, Accountable, Flexible, Efficient Transportation Equity Act: A Legacy for Users (SAFETEA-LU), being signed into law on August 10.

[14][15][16] The I-26 Connector in Asheville will relocate Interstate 26 across the French Broad River, convert Patton Avenue along Bowen Bridges to local traffic and reroute I-240 along I-26 further north.