The victim was driving east in the westbound express lanes and collided head on with a tractor trailer just before 3 a.m. in Springfield.
The driver was crushed in the vehicle, a Volkswagen Gulf, and pronounced dead at the hospital.
The driver of the tractor trailer was treated for minor injuries.
It was not clear why the victim was driving in the wrong direction.
The westbound express lanes were closed for more than four hours for the investigation.