The incident happened sometime before noon on the westbound 10 connector to southbound 215 in San Bernardino County.
The unidentified victim was ejected from the truck when the vehicle jackknifed on the ramp and hit a guardrail.
The driver then plummeted several dozen feet to road below and was pronounced dead at the scene.
Video of the incident showed the driver covered with a tarp as California Highway Patrol officers investigated.
The crash happened during a storm that deluged Southern California with several inches of rain, but it was not immediately known if weather played a factor.
No further details were available.
Rain was blamed for several crashes across the region, including one on Interstate 5 N in Glendale that flipped a semi and tied up traffic for hours.