The drivers were stuck near Tejon Pass, which rises above 4,000 feet and is frequently closed by winter storms. Interstate 5, a main artery between northern and southern California, was shut down.
An estimated 300 to 500 trucks and cars were stuck overnight in a 40-mile stretch of the highway, but most were guided out by morning, said California Highway Patrol Officer Mark Ehly.
"We were taking cars out pretty much one at a time" through the night, he said.
It was not clear when the road would reopen. More snow and sleet was expected to fall on the area through the day.
One driver said that he had been stuck for 24 hours, unable to move because highway patrol officers had blocked the road. Early Thursday, patrol officers were escorting motorists down from the pass but television footage showed dozens of commercial trucks crowding parking lots to wait out the weather.
Elsewhere, heavy rain littered roadways with jackknifed trucks, flipped cars and vehicles that had been in fender-benders. There were about 125 crashes on Los Angeles County freeways overnight, patrol Officer Francisco Villalobos said.
Flash flood watches were issued for Southern California areas burned bare by last fall's wildfires, but only minor mudslides were reported.
Overnight, the storm dumped nearly 7 inches of rain in some areas of Ventura County, and 4 inches or 5 inches elsewhere. Santa Barbara's airport got 4.16 inches of rain, breaking the record of 2.45 inches for the day set in 1943.
Another storm - this time a warmer one coming up from Mexico - was expected to arrive Thursday night and dump up to an inch of rain in Los Angeles but less snow, said National Weather Service specialist Stuart Seto.