It happened just before daybreak near the community of Wilton somewhere just west of NC Hwy 96.
The North Carolina Highway Patrol told ABC11 Eyewitness News 54-year-old Valerie Hyers crossed the center line and was hit head-on by the tractor-trailer. She died at the scene.
Pictures from Chopper 11 HD showed the truck on its side beside the highway and firefighters using the Jaws of Life to cut the occupants of the car out of the wreckage.
Some wheels of the truck were shorn off by the impact and it appeared the truck's diesel tanks were ruptured, because there was a long stain on the pavement that ended where the truck came to rest.
The truck driver was taken to Granville Medical Center with minor injuries. The wreck shut down NC 56 for several hours.
The truck appeared to belong to a company in Virginia that distributes fiberglass insulation and other building products, but that was not confirmed.
The investigation continues.