Durham Police said 26-year-old Victoria Lynn Jones, of Graham, died in the crash.
The crash happened between the exits for NC Highway 54 and Highway 751 just after 4 a.m. Durham police said Jones was driving a 2014 Honda CR-V heading west in the eastbound lanes when she collided into a tractor-trailer.
The 34-year-old truck driver did not suffer any visible injuries, police said.
An unoccupied Durham police car was also hit at the scene. There were no injuries from that crash.
Jones' sister told ABC11 that her family is devastated, saying "they are heartbroken over this tragic accident."
The accidents caused lane closures and heavy delays, shutting down that stretch of I-40 for nearly six hours.
The crash remains under investigation.