Two people suffered minor injuries, authorities said Friday.
The fire started in the Cajon Pass along Interstate 15 — the main highway between Southern California and Las Vegas — and quickly chewed through bone-dry brush.
As flames closed in, drivers and passengers ran from their vehicles.
Lance Andrade, a 29-year-old railroad conductor from Apple Valley, was stopped in traffic when the fire jumped the freeway and panicked people started running toward him.
He also ran, but with flames all around, there was nowhere to go.
A firefighter told everyone to take cover. Andrade, four other men, and two elderly women got inside the back of a semi-truck.
One of the women had been separated from her family began crying, and everyone was terrified.
"You could hear the explosions from people's vehicle tires popping from the heat," Andrade said.
"You could hear crackling, smoke was coming in every direction, you could feel the heat. We just waited it out and prayed to God."
Russell Allevato, 45, of Southgate, Michigan, was traveling from Las Vegas to Los Angeles with his two teenage daughters, his nephew and his nephew's girlfriend.
"It was total smoke and all the cars just started to stack and the fire got closer to us, and everyone started running up the hill," he said.
"Hundreds and hundreds of people running up the hill."
Their rental car was among those destroyed.
"All our stuff was charred and gone," Allevato said by phone as he rode in the back of a California Highway Patrol vehicle.
Television helicopters carried the scene live as the flames leapt from vehicle to vehicle while water-dropping helicopters and then firefighters on the freeway battled to get control.
A car-carrying tractor-trailer and a boat were among the losses left smoldering on the highway.
Dozens of vehicles were abandoned, and hundreds of others turned onto side roads in the rugged area about 55 miles northeast of Los Angeles.
"It's crazy, you're watching black clouds and white clouds of smoke, there's a ridgeline off to my right ... and it looks like any second flames will come over the ridgeline," Chris Patterson, 43, said from his vehicle.
As firefighters gained control on the freeway, the flames spread to 3,500 acres and burned at least five homes in the rural community of Baldy Mesa. About 50 more were threatened.
Melissa Atalla said she could see the flames from her gas station.
"People are spectating from our parking lot, running around getting water and beer.
It's chaos," Atalla said. "One man came in and said, 'Oh my. My house is getting burned.' "
An evacuation center was set up at the local high school as firefighting equipment flooded the area.
There were 22 engines, six air tankers, three helicopters, a bulldozer and hundreds of firefighters.
California is in the midst of severe drought, and wildfires are common. Some break out near freeways, but it's very unusual to have vehicles caught in the flames.
On Friday, the 15 freeway was typically busy about 2:30 p.m. when the fire started near the northbound lanes.
With temperatures in the mid-90s and winds kicking up, it quickly ran up a hill and across the southbound lanes before any help could arrive.
Vehicles that had slowed came to a stop as the flames approached. Occupants fled.
"There were elderly trying to get up the hill. People had animals, dogs.
They tried to get their dogs out of the car," Allevato said.
His 15-year-old daughter, Leah, cried about her lost vacation.
"We waited two years for this vacation, and I saved all my money," she said.
"I was thinking about it every day, and I finally got here and I have no clothes. ... I waited so long, and it's ruined."