A cold storm could hit the region as soon as Tuesday night, with moderate rain beginning Wednesday morning and lasting until the weekend.
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The storm will bring the threat of isolated thunderstorms capable of brief heavy downpours and small hail, according to the National Weather Service. The NWS says areas near the Grapevine could see a snowfall total of as much as 3 to 6 inches.
More: Latest SoCal forecast
NWS officials warned the wet weather could bring major travel delays and road closures.
Snow and ice could impact travel around the 5 Freeway near the Grapevine, and road closures could also affect Highways 14 and 33.
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"Hydroplaning is something that happens very often and people are just not ready for it," said Officer Roberto Gomez, a spokesman for the California Highway Patrol. "Keep control of your vehicle - do not apply your brakes. Let the vehicle slow down, foot off the accelerator and try to control your vehicle."
Motorists traveling through the Cajon Pass could also be impacted by the storm, causing a potential nightmare for those traveling to and from Las Vegas.
Recent burn areas are also at risk of flooding and debris flow, the NWS said.
According to the Automobile Club of Southern California, the worst time to travel in Southern California is Wednesday evening between 5 p.m. to 7 p.m.
Nearly 4 million people in the Southland plan to travel by car this Thanksgiving, with Las Vegas as the top destination.
AAA is anticipating about 100,000 vehicle breakdowns throughout the state Wednesday through Sunday. Nationwide, some 368,000 breakdowns are expected.
The top three causes are dead batteries, flat tires, and locking yourself out.