According to the Nebraska State Patrol, a van traveling east left the road at mile marker 268, hitting a semi parked in the rest area there.
The driver, 27-year-old Maurice Lewis, from Chicago, was killed.
Troopers said two passengers, 48-year-old Willie Sheppard and 22-year-old Charles Stokes, from Missouri, were both transported to Good Samaritan Hospital.
Stokes has since been released, but Sheppard remains in critical condition.
The truck driver was not transported to a hospital.
Troopers said both Sheppard and Stokes were wearing seatbelts.
The rest stop between Kearney and Overton was shut down during the investigation.
It is not known why the driver left the road.