LOS ANGELES—Portions of the heavily populated Hollywood neighborhood were ordered to evacuate Wednesday evening as a new fire broke out in the hills above the center of this city battling numerous deadly blazes.

At least five people were dead and tens of thousands were forced to evacuate as six wildfires simultaneously hit the most populated county in America and stretched the region’s firefighting resources to its limits.

A wind-fueled fire devastated the affluent oceanside Pacific Palisades neighborhood while another, responsible for all five deaths, burned in and around Pasadena to the east of Los Angeles.

Flames rise from a structure as the Palisades fire burns during a windstorm on the west side of Los Angeles, California, U.S. January 8, 2025. REUTERS/Ringo Chiu

Officials said the disaster in this county of 10 million people was unprecedented and the result of a combination of deadly weather conditions .

“This firestorm is the big one in magnitude,” L.A. Mayor Karen Bass said Wednesday evening. “Hurricane-force winds are usually accompanied by rain storms. But these are hurricane-force winds that are combined with extremely dry drought conditions.”

She warned that the region would continue to face strong and erratic winds that could spread the blazes further during the night.

The Hollywood Hills brush fire broke out as local officials were holding a press briefing Wednesday, prompting the city fire chief to leave early. The 10-acre blaze was burning in a popular hiking trail near the Hollywood sign.

The Palisades fire, which destroyed more than 1,000 structures and left entire neighborhoods in ruins, was 15,800 acres and growing Wednesday evening, Los Angeles Fire Department Chief Kristin Crowley said. Two elementary schools in the area were destroyed, as was 30% of the Palisades’ high school.

The Eaton Fire in the Pasadena area, which also damaged or destroyed more than 1,000 structures, was 10,600 acres and growing Wednesday evening, Los Angeles County Fire Chief Anthony Marrone said.

Both fires were completely uncontained Wednesday evening. More than 130,000 people affected by them were ordered to evacuate or warned they should prepare to evacuate soon.

All schools in the Los Angeles Unified School district, the second largest in the country, were ordered closed Thursday due to fire danger and noxious smoke affecting much of the region. Bass asked residents to stay off the roads unless they were evacuating.

Another blaze—dubbed the Lidia Fire—also started Wednesday afternoon in part of the Angeles National Forest north of the city and grew to 80 acres by the early evening.

Winds littered much of L.A. with palm fronds, ash and debris, while some streets were lined with cars abandoned by people trapped in gridlock traffic and desperate to flee. Hundreds of thousands are without power.

The wind whips embers as the Palisades fire burns during a windstorm on the west side of Los Angeles, California, U.S. January 8, 2025. REUTERS/Ringo Chiu TPX IMAGES OF THE DAY

The out-of-control wildfires are hitting some of the most famous stretches in the country and have devastated luxurious homes, threatened neighborhoods and disrupted the lives of millions of people.

A Los Angeles Fire Department spokesman said a 25-year-old female firefighter suffered a serious head injury. Three people were arrested for looting, according to the L.A. County Sheriff.

The fight against the Palisades fire was slowed when 20% of approximately 1,000 hydrants in the area ran out of water. Janisse Quiñones , chief executive of the Los Angeles Department of Water and Power, said high winds made it impossible for firefighters to combat the blazes from the air, forcing them to rely on hydrants that are typically used to combat single-home blazes.

Three water tankers in the Palisades, which were each filled up with one million gallons of water on Monday night, ran out and couldn’t be refilled because the firefighting efforts would have needed to be paused.

“We tried three contingency plans and they all failed because in hazardous conditions, the crew had to be evacuated,” Quiñones said Wednesday evening. “We have not given up and expect to have a solution soon.”

President Biden, who has been in Los Angeles this week, visited a fire station in Santa Monica on Wednesday.

“We’re doing anything and everything and as long as it takes to contain these fires,” Biden told reporters in Los Angeles. “It’s going to be a hell of a long way. It’s going to take time.”

Later in the day he canceled a planned trip to Italy to deal with the disaster.

Jamie Sherrill , a registered nurse who specializes in aesthetics and is known to her star-studded clientele as “Nurse Jamie,” said she lost her home in the Palisades.

Sherrill said she worked for years to build her life in the area and anticipated her triplets would attend the nearby high school one day. On Tuesday, she rushed to gather her family and flee.

“I got mismatched shoes, a passport, some photos, a couple things of clothes…I have an empty suitcase,” she said. “My kids are 13 and it was just hysterical, not in a good way.” The family stayed in a hotel overnight and are now with friends, she said. She’s now packing up her Brentwood spa, which she said is on the cusp of an evacuation zone.

Firefighters battle the Palisades Fire as it burns during a windstorm on the west side of Los Angeles, California, U.S. January 8, 2025. REUTERS/Ringo Chiu

“We are heartbroken and unsure what will be left,” the Reel Inn, a 36-year-old popular seafood restaurant along the Pacific Coast Highway in Malibu, wrote in a social-media post late Tuesday as the Palisades fire spread across the area.

Much of Hollywood including major studios operated by Disney , Warner Bros. Discovery and NBCUniversal shut down production on their lots as a result of the fires. Studios canceled movie premieres for the Ryan Gosling -produced horror movie “Wolf Man” and “Better Man,” the film about British pop star Robbie Williams . Jimmy Kimmel ’s late-night show on ABC, which airs from Hollywood, was canceled for Wednesday night. At the Universal lot, shows including the Max comedy “Hacks” stopped production. The Critics Choice Awards ceremony slated for Sunday was postponed to late January.

Many Los Angeles landmarks including Griffith Park and the city zoo were closed Wednesday. The National Hockey League postponed an evening Los Angeles Kings game.

“We are not out of danger,” Crowley said Wednesday evening. “You can see the active fires with strong winds that are going to continue.”

The causes of the fires are unknown and under investigation.

California Gov. Gavin Newsom declared a state of emergency Tuesday and the state has secured federal assistance from the Federal Emergency Management Agency.

Officials said firefighters from nearby states including Arizona, New Mexico, Nevada, Oregon, Washington and Utah were being activated to assist.

Destructive wildfires were primed to explode from what fire officials call a perfect storm of dry vegetation and high winds blowing flames into heavily populated areas. But what makes these fires so unusual is its timing, in January, when the California rainy season typically extinguishes the threat of infernos until spring.

This year, however, Southern California has been off to one of its driest seasons on record. Downtown Los Angeles has received just 0.16 inch of rain since Oct. 1, compared with a normal total of 4.56 so far, according to the National Weather Service. Northern California, by contrast, has received a bounty of rain and snow.

The fire threat has increased greatly in California and other parts of the West amid a hotter and drier climate and an expansion of homes into the wildland areas surrounding major cities. Sixteen of the 20 most destructive fires on record in California have broken out in the past decade, according to Cal Fire.

Write to Gareth Vipers at gareth.vipers@wsj.com and Sarah Krouse at sarah.krouse@wsj.com

Corrections & Amplifications undefined Downtown Los Angeles has received just 0.16 inch of rain since Oct. 1, compared with a normal total of 4.56 so far, according to the National Weather Service. An earlier version of this article incorrectly said it had received 16 inches of rain. (Corrected on Jan. 8)