Approximately 60,000 fans are expected to pour into Chapel Hill for the game, which kicks off at 8 p.m.
They will be contending on Interstate 40 with typical rush-hour traffic and visitors headed to Canned Food Night at the North Carolina State Fair.
The traffic problems could go straight into the heart of Chapel Hill. Kenan Memorial Stadium is nestled in the center of campus and backs up against UNC Hospitals.
"We're trying to impress upon people to make sure they allow enough time to get where they're going. Expect delays coming into town as well," Chapel Hill Police Lt. Kevin Gunter said.
Motorists traveling from Raleigh can use U.S. Highway 64 to U.S. Highway 15/501. Motorists from Durham can take U.S. 15/501, exit onto Columbia Street, then turn onto Manning Drive.
Gunter said extra patrols are on duty to help keep the delays at a minimum before and after the game.
Three times as many university and hospital employees will be working Thursday than they usually do on Saturday games, so less than half of the parking spaces normally used for game parking will be available.
UNC Hospitals is closing its clinics early, and all UNC employees will be dismissed two hours early, at 3 p.m. Towing from some parking lots will begin as early as 3:30 p.m. to open them for game traffic.
State law requires UNC employees to make up the hours. University officials said employees can add the hours onto another work day or use vacation or furlough time.
Throughout the evening, hospital staff, patients and visitors have priority for parking. Campus lots opened for game traffic at 5:30 p.m. Municipal parking lots and decks will be open as usual. Most public parking is on the South Columbia Street end of Manning Drive.
Access to some streets and residential areas in Chapel Hill will also be restricted.
The game was scheduled during UNC's fall break to reduce traffic congestion and to avoid interfering with classes.
ESPN, which is broadcasting the game, agreed to a later kick-off time than most other Thursday night games to help with traffic.