Interstate 85 provides the major transportation route for the Upstate of South Carolina, linking together the major centers of Greenville and Spartanburg with regional centers of importance. In South Carolina, Interstate 85 bypasses Clemson and Anderson on the way to Greenville. Beginning at Anderson, I-85 widens from four to six lanes. Near Powdersville, U.S. 29 joins I-85 and they run concurrently until they cross the Saluda River. Interstate 85 bypasses just south of Greenville, but provides two links into the city via spur routes Interstates 185 and 385. I-85 also bypasses Greenville-Spartanburg International Airport, which serves the Greenville-Spartanburg metropolitan area. I-85 then bypasses the city of Spartanburg to the north where its original route is now signed Business Loop 85 and was approved by AASHTO on April 22, 1995. Near mile marker 70, I-85 intersects with I-26. The exits are signed as exits 70A for east-bound traffic and 70B for west-bound traffic. North of Spartanburg, I-85 narrows from six lanes back to four lanes and bypasses Gaffney. Much of the terrain between Spartanburg and the North Carolina border is rural in nature.
In North Carolina, I-85 enters a relatively rural area near Kings Mountain before entering the Gastonia and Charlotte areas. In Charlotte, I-85 bypasses Charlotte-Douglas International Airport and turns northeastward just before reaching uptown Charlotte; thus I-85 just bypasses uptown to the north where it junctions with Interstate 77. North of Charlotte, the highway passes near Concord, Salisbury, Lexington and High Point before reaching Greensboro. At Greensboro, I-85 shifts away from downtown Business I-85 (old I-85 through town). I-85 then joins I-40 east of downtown, and the two highways are cosigned as they pass through Burlington, Graham and Mebane then separate near Hillsborough where I-40 turns toward Chapel Hill, Cary and Raleigh. From Durham, I-85 turns northeastward and heads toward Virginia.
Before a 2010 decision to raise the speed limit in the state to 70, Virginia's portion of I-85 was also the only Interstate Highway in the state with a posted speed limit greater than 65 miles per hour (105 kilometers per hour). It was raised from 65 mph (105 km/h) to 70 mph (113 km/h) on July 1, 2006, by the state legislature.
In 2004, I-85 was rerouted around Greensboro; and it split with I-40 eight miles (13 km) east of the original departure point. I-40 ran with I-85 along the bypass to the southern/western end and I-40 continued on a new freeway alignment at Exit 121 until September 2008, when it was rerouted back to its old alignment through the city. Despite its reroute around Greensboro, the overall length for I-85 in North Carolina (233 miles/373 km) remains the same as before.
An extension of Interstate 85 is proposed west from Montgomery to interchange with Interstate 20 & Interstate 59 just east of the Mississippi state line., where it will connect with I-20 and I-59 near Cuba, Alabama. This extension will roughly follow the route of U.S. 80, going through or bypassing Selma and Demopolis. The FHWA approved the alignment on February 17, 2011 after AASHTO approved at its Fall 2010 meeting in Biloxi, Mississippi. Also approved was the proposal to re-designate part of existing I-85 south and east of Montgomery to be bypassed as part of the extension of I-85 as I-685. Alabama has permission to co-sign this part of I-85 as I-685 until the new alignment is built. This section is also envisioned by some as part of a proposed Interstate 14.