State fire director Ken Pimlott said winds that eased in the afternoon could return with gusts up to 80mph on Thursday that would make it impossible to fight the fire.
"The greatest threat is and continues to be the wind", he said, noting that the Santa Ana winds are expected to keep blowing through Friday.
Huge, fast-spreading wildfires in southern California have already destroyed at least 200 homes.
The blaze, dubbed the Creek Fire, was reported at 3:42 a.m.in the area of Gold Creek and Little Tujunga roads, according to the Los Angeles County Fire Department, which was assisting the U.S. Forest Service and the Los Angeles Fire Department in the battle.
Officials said the flames have destroyed almost 200 homes.
Some 350 firefighters - 52 engines - were on the Skirball Fire, which had burned at least four homes and possibly six by 9:30 a.m.
The number of destroyed structures was unknown due to the intensity of the fire, but officials had estimated about 150 buildings early Tuesday.
California Gov. Jerry Brown declared an emergency for Ventura County, freeing state resources such as the National Guard to support response efforts.
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It is one of the smaller of several wildfires burning in the Los Angeles area, but it is in a relatively densely populated area that includes the tony neighborhood of Bel Air and borders the campus of UCLA. The Los Angeles County Fire Department awoke the Padilla family at around 4 a.m., ordering them to evacuate immediately. Officials will provide an update Thursday morning as to when evacuated residents might be able to return to their homes, he added.
"The embers from the trees were dropping on our cars", said Mary Robinson, a Ventura resident, who fled Monday night.
"Now, everything that I have, except for my lovely family, is gone", she said.
Santa Ana winds continued to hamper the firefighting effort, with gusts expected to reach up to 80 miles per hour at their peak.
Satellite images show how fast it lit up neighborhoods at night.
Upton of Cal Fire said she can not remember any time when so many wind-driven fires were burning at the same time this late in the fire season.
"This is the start a multiple-day weather event so we're not through this yet", Los Angeles Police Chief Charlie Beck told reporters at a briefing.