Authorities issued a "purple" alert -- never used before -- because of the extreme danger, warning that winds could reach 128km/h severely limiting firefighting efforts.
The biggest and most destructive of the windblown fires raking Southern California shut down one of the region's busiest freeways on Thursday and threatened Ojai, a scenic mountain town dubbed "Shangri-La" and known for its boutique hotels and New Age spiritual retreats.
San Diego County officials also ordered mandatory evacuations due to another fast-moving fire fanned by Santa Ana winds.
California state fire authorities said in a statement that a wildfire had destroyed two buildings and damaged 12.
In Ojai, 7,000 residents were warned to clear out and patients unable to walk were moved from the Ojai Valley Community Hospital because of unprecedented, hurricane-force Santa Ana winds in the overnight forecast.
The winds turned out to be less fierce than expected, but firefighters still had to contend with gusts that fanned the fire to 388 square kilometres and put thousands of homes in jeopardy.
Down along the coast, fires flared along US Highway 101, forcing an evacuation of the tiny community of Faria Beach.
"Anyone in your homes still, you need to leave now," a California Highway Patrol officer said through a loudspeaker while driving down a smoke-shrouded street. "The fire is here, you need to leave."
TRT World's Tetiana Anderson reports.
The highway, which runs the length of the state and is a major commuter corridor to Los Angeles, was closed intermittently along the 45 kilometre stretch between Ventura and Santa Barbara.
The Ventura County blaze and three other major fires burning in the Los Angeles area have put tens of thousands of people under evacuation orders and destroyed nearly 200 homes and buildings, a figure almost certain to rise.
In the San Fernando Valley north of Los Angeles, the Creek Fire destroyed at least 30 homes, blackened more than 4,800 hectares and forced the evacuation of 2,500 homes and a convalescent centre.
Another fire, known as the Rye Fire, threatened more than 5,000 homes and structures northwest of Los Angeles.
The Skirball Fire, which erupted early on Wednesday had burned about 200 hectares near large estates in the Bel-Air neighbourhood of Los Angeles, was only 5 percent contained.
Firefighters battled to save multimillion-dollar homes in the path of the flames.
"These are days that break your heart," Los Angeles Mayor Eric Garcetti said during a news conference. "These are also days that show the resilience of our city."
TRT World's Kerry Alexandra reports.
No civilian casualties or fatalities have been reported. Three firefighters were injured and hospitalised in stable condition, the Los Angeles Fire Department said.
Dozens of schools across the area cancelled classes on Thursday.
The largest blaze, the Thomas Fire, burned more than 90,000 acres (36,000 hectares) after it destroyed more than 150 homes and threatened thousands more in Ventura, about 50 miles (80 km) northwest on Los Angeles.
Additional evacuations were called for late on Wednesday in the Ventura area, where 50,000 people had already fled their homes over the last three days.
"The danger is imminent," Cal Fire said in its evacuation notice.