Exit numbers in Tennessee were formerly numbered backwards, increasing from east to west, because the road was formerly U.S. Route 23 and Interstate 181, two north-south roads. This exit numbering was changed to the correct way in March 2007 when exit numbers were changed on all 284 signs along the I-26 route; the remaining I-181 signs north of I-81 were also replaced by I-26 signs at that time. The old exit numbers will be displayed on signs with the new ones until March 2009.
About 20 miles after Spartanburg one reaches the foothills of the Blue Ridge Mountains. After crossing the North Carolina border into Polk County, I-26 junctions the limited access freeway U.S. Route 74 near Columbus and heads up a 6% grade for the next three miles through Howard Gap. Then it passes over the highest bridge in North Carolina, the Peter Guice Memorial Bridge, 225 feet above Green River between Saluda and Flat Rock in Henderson County and crosses the Eastern Continental Divide at an elevation of 2,130 feet, having climbed from around 1,100 feet at the U.S. Route 74 interchange. The land flattens substantially after entering the French Broad River basin from Flat Rock to Hendersonville, Fletcher and Arden. For all practical purposes, I-26 ends at the junction with I-40 in Asheville; however the Future I-26 may be brought up to Interstate standards very soon. Between Mars Hill and the Tennessee state line, the new section of Interstate is a designated North Carolina Scenic Highway. It climbs from 2,200 feet in elevation to 3,800 feet in elevation at Sams Gap; two major climbing sections exist along this stretch along with major cuts through the mountains and the 220-foot Laurel Creek Gorge Bridge. The North Carolina Welcome Center, encountered when traveling Eastbound, has an overlook with views of the highest mountain range on the East coast, the Black Mountains. The Appalachian Trail passes under the Interstate at Sams Gap as well.
Beginning in the city of Charleston, South Carolina, I-26 travels northwest over mostly flat plains with little urbanization (and fewer traffic jams) past North Charleston. After the junction with I-95 just inside of Orangeburg County, the terrain becomes somewhat hilly. Orangeburg is the first major stop outside Charleston with several exits bearing its name. Between Orangeburg and the junction with I-77 just outside of Cayce the road goes up and down a few very long hills averaging about 100 feet high. After I-77 comes is the Columbia metropolitan area to which I-26 offers good shopping and dining access. The metropolitan area ends after Exit 101, past which the terrain becomes hilly once again. The next major city is Spartanburg, where I-26 junctions the I-85 corridor, popular for international business.