The fast-moving fire forced nearly 85,000 residents of San Bernardino County to evacuate, according to the wildfire’s federal InciWeb page.
Fire authorities warned of "imminent threat to public safety" as 0% of the fire had been contained.
The massive fire, which is being called Blue Cut, prompted Gov. Jerry Brown to declare a state of emergency in the area.
The blaze started about 10:30 a.m. Tuesday in Cajon Pass, a mountain pass between the San Bernardino Mountains and the San Gabriel Mountains. The area is about 70 miles east of Los Angeles.
An estimated 34,500 homes are affected by the evacuation warnings which affect Cajon Pass, Lytle Creek, Wrightwood, Oak Hills and surrounding areas. Seven hundred firefighters have been sent to the area.
As flames continue to spread rapidly, crews face another difficult day in the firefight while they work to contain the massive blaze.
Hot, dry and breezy conditions are forecast, and a red flag warning was scheduled to last for the next several days, according to Incident Commander Mike Wakoski.
Temperatures are forecast to top 100 degrees in the fire zone, with humidity falling below 10 percent, he said at a morning news briefing. Wakoski described the fuels as “extremely dry” and “very explosive.”
The fire quickly scorched up the dry hills as winds carried the embers. It fed on the thick, parched brush, and engulfed an unknown number of homes and structures, according to fire officials.
One resident told CNN affiliate, KABC that she was there when the flames were all around.
"We had to keep the windows up because we couldn't breathe. The smoke was so thick, and as soon as the smoke cleared, we could see that everything was gone," Crystal Armstrong, who lost her home in the fire, said.
Firefighters implored residents to evacuate, saying that refusing to do so puts their lives and other people's lives at risk.
Aerial views showed the mountains covered in plumes of smoke.
The out-of-control fire also destroyed the landmark Summit Inn Restaurant in Oak Hills on Tuesday afternoon.
Video showed the flames consuming the well-known restaurant, located at the crest of the 15 Freeway.
For 60 years, the roadside diner has been a familiar sight for those traveling along historic Route 66, according to the restaurant's website.
“As of right now we’re fortunate to say we have not suffered any loss of life to civilians or firefighters,” Sherwin said Wednesday morning.
Dozens of big rigs packed the Pilot Travel Center in Hesperia on Wednesday as drivers waited for the 15 Freeway to reopen.
The freeway was shut down in both directions Wednesday. The northbound lanes were closed at the 215 Freeway, while southbound traffic was stopped at Ranchero, according to the information website.
There was no estimate on when the closure would be lifted.
Mandatory evacuations were ordered for about 82,640 people in more than 30,000 residences, including the entire community of Wrightwood.
Evacuation centers were open at the Jessie Turner Community Center, located at 15556 Summit Avenue in Fontana and at Sultana High School, located at 17311 Sultana Street in Hesperia.
Several shelters were also available to those with large and small animals.