It happened at about 6:15 a.m. Monday morning on Highway 145 and Barstow, just south of the Fresno County line.
The Highway Patrol says the driver of a Chevy pickup was headed southbound when it crossed over the center divide and hit a big rig truck travelling northbound. Both vehicles immediately caught fire.
The driver of the pickup was killed by the impact. Officers say the driver of the big rig climbed out just minutes before the cab erupted in flames.
Caltrans shut down the highway for several hours while firefighters put out the fire and crews cleared the roadway. The CHP said speed was likely a factor in the crash.