It happened just after 4:15 a.m. Thursday on Route 322 between N. Birdell and Cambridge roads in Chester County, Pennsylvania.
The driver of the car was trapped and had to be extracted, and later died at the hospital.
Chopper 6 was over the scene of the crash, where both front ends of the vehicles involved could be seen with heavy damage.
Driver killed after crash with semi truck on Route 322 in Honey Brook, Township, Pa.
Rt. 322 was closed for an extended period of time but has since been reopened.
The accident is under investigation.
RELATED: Check the 6abc Neighborhood Safety Tracker