The North Carolina Highway Patrol responded to the accident around 11:30 a.m. near the intersection of Highway 421 and South Main Street, south of Goldston.
The Highway Patrol said a 2002 Buick Lasabre heading north on Highway 421 crossed the line and struck the tractor-trailer head-on. The driver of the car, Marguerite Temple, 73, died on impact.
The driver of the truck, Edmond Wade, was not seriously hurt and was not taken to the hospital.
No charges will be filed in the accident, the Highway Patrol said.
Thursday's accident marks the third deadly wreck on the highway.
"It's puzzling to us why these collisions are still occuring, but we're going to keep on evaluating what we're doing down there, and if we need to, we'll bring more troopers in," said Lt. Everett Clendenin, of the state Highway Patrol.