The blaze erupted during morning rush hour along U.S. 101 in the Camarillo area about 50 miles west of Los Angeles. It was quickly spread by the winds, which also pushed other damaging blazes across the region.
The evacuation orders included the smoke-choked campus of California State University, Channel Islands, attended by about 5,000 students.
Flames quickly moved down slopes toward subdivisions, according to the Ventura County Fire Department. Some 6,500 acres -- more than 10 square miles -- were charred, with no containment. A cluster of RVs in a parking lot was destroyed as flames moved close to a mobile home park. There were no reports of homes burning.
More than 500 firefighters from multiple agencies with help from aircraft dropping water and retardant worked to protect numerous homes around Camarillo Springs Golf Course and in a section of adjacent Thousand Oaks.
Air tankers had to be grounded in early afternoon because of the winds, which gusted to 50 mph.
"We're at mother nature's mercy right now," county fire spokesman Tom Kruschke told KABC-TV.
The Santa Ana winds sent plumes of smoke and embers over the homes and strawberry fields to the south. At midday, farm sheds burst into flames in a clearing amid rows of crops.
The vegetation-withering dry winds out of the northeast caused humidity levels to plunge from 80 percent to single digits in less than an hour. Temperatures soared into the 90s in Camarillo.
The area is at the western edge of the Santa Monica Mountains, which abruptly descend to a coastal agricultural plain. It was possible the flames could burn all the way to the Pacific Ocean, about 10 miles from the start point. The California Highway Patrol closed a 10-mile stretch of Pacific Coast Highway at Point Mugu.
Freddy Aoygio watched flames creep to within about 30 feet of her back door in the Camarillo Springs area. She had packed important papers and photos in her car in case she was ordered to leave.
"We'll keep our fingers and toes crossed," she told the Ventura County Star. "That's all we can do."
About 100 miles to the east, two homes, a number of outbuildings and several vehicles were destroyed, and two other homes were damaged in a 5-acre grass fire that prompted the evacuation of an elementary school in Jurupa Valley, said Theresa Williams, a spokeswoman for CalFire.
The blazes could signal a difficult fire season ahead.
Officials with the National Interagency Fire Center in Boise said Wednesday in their first 2013 summer outlook that a dry winter and expected warming trend mean the potential for significant fire activity will be above normal on the West Coast, in the Southwest and portions of Idaho and Montana.
Meanwhile, the California Department of Water Resources found the water content in the snowpack was just 17 percent of normal. The snowmelt is a vital water source for the state.
Elsewhere in California, crews made progress overnight on a 4 1/2-square-mile fire burning in the foothills of the San Bernardino Mountains north of Banning, but winds returned on Thursday morning, Riverside County fire spokeswoman Jody Hagemann said.
The fire that burned a home on Wednesday was 40 percent contained with only sporadic flames showing, but renewed winds gusting to 40 mph could halt that progress.
The blaze was being fought by aircraft and nearly 700 firefighters. Two firefighters suffered minor injuries.
Hundreds of people briefly evacuated homes.
A stand from firefighters came too late for Joe Kiener, 53, who lost the house he had lived in since his mother bought it in the 1970s.
Kiener was home on a lunch break when he stepped outside to check on his barking dog and saw heavy smoke approaching. He took the dog and started to leave just as a deputy arrived to tell him to evacuate.
"When I left I went around the corner and I got engulfed in a big cloud of smoke," said Kiener.
He got out safely, but the next time he saw the house was in a cellphone picture sent by his neighbor. The roof was on fire, and he knew it would be destroyed, but he shrugged off the loss.
In Northern California, crews were able to hold the line against two wind-whipped wildfires, but one in Tehama County continued to grow.
The Panther Fire north of the town of Butte Meadows had spread to 2,000 acres with 10 percent containment. The fire was burning in a remote area of brush and timber and is not threatening any homes, state fire spokesman Daniel Berlant said.
A fire in Sonoma County that has burned 125 acres did not grow overnight. Full containment on the Yellow Fire was expected later in the day, Berlant said.
Two smaller fires totaling 165 acres were burning in Glenn and Butte counties. Berlant said crews were also able to hold the line against one of those fires, the 55-acre Cedar Fire in Butte County, but wind was expected to be a factor.
Weather forecasts called for red flag conditions of extreme fire danger in canyons, foothills and mountain passes because of the winds, coupled with hot, dry weather.
Several other small fires were reported in widely separated areas near freeways.
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