The mercury was forecast to top out at a scorching 113 Fahrenheit (45 Celsius) in parts of Los Angeles later in the week, marking the high point of an already hot summer.
Meteorologists say a ridge of high pressure could push temperatures 20 degrees higher than usual for this time of year in some places, with dangerous conditions expected for several days.
The National Weather Service said an excessive heat warning would be in place from lunchtime on Wednesday until after sunset on Friday.
The Woodland Hills area of Los Angeles, a well-to-do neighborhood northwest of downtown, was expected to be the hottest part of LA County.
Los Angeles Mayor Karen Bass ordered the opening of cooling centers throughout the city where people who may not have access to air conditioning will be able to take shelter.
Although not quite as high, the soaring temperatures will also affect coastal areas, which usually escape the worst of the heat and have enjoyed a relatively balmy August.
Climate scientist Daniel Swain said the next few days will be a taste of what inland areas of the state have already endured.
"Most of California's immediate coastline missed out on record heat this season (including some of the most densely populated portions of the SoCal megalopolis)," he wrote on his Weather West blog.
That means "that while a majority of California's land area did indeed just experience a record-hot summer, the majority of California's population likely did not."
Death Valley -- routinely one of the hottest places on Earth -- is likely to see the mercury hit 118 Fahrenheit, though that is slightly lower than the almost 122 F it saw in July.
Further inland, the heat will also affect parts of Arizona, including Phoenix, where Tuesday marked the 100th day in a row that the temperature had topped 100 Fahrenheit.
And there was no respite in sight for the state's biggest city, with blistering heat expected throughout the week.
High temperatures in the southwestern US -- much of which is desert -- are not unusual at this time of year.
But scientists say human-caused global warming is pushing norms higher, and creating more unstable weather patterns.
