The semi had overturned, but it was not carrying anything hazardous - just shoes.
Lanes were closed for several hours, but officials were able to reopen all lanes by 5:40 a.m. before heavy morning traffic.
The California Highway Patrol said the driver of the Mustang fled the scene. He is described as a black male adult in his 30s.
The cause of the collision has not yet been determined. Anyone with information is urged to call CHP at (714) 892-4426.