The freeway was partially reopened by Thursday afternoon but drivers were urged to use caution while traveling through the area as firefighting efforts were continuing in the area.
Many of the evacuations were lifted early Thursday morning and all of them were lifted by Thursday evening, firefighters said.
Containment by Thursday evening was estimated at 27%.
The Route Fire started around noon Wednesday near the 5 Freeway at Lake Hughes Road. With triple-digit temperatures and thousands of acres of dry brush on the ground, it spread quickly during a Southern California heat wave that is forecast to last into next week.
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Evacuations ordered as brush fire spreads to 4,600 acres in Castaic area, closes 5 Freeway
"The fire behavior and what you saw yesterday should be a wakeup call to us about the potential... that we're entering into over the next few days in terms of the fire conditions," said Fire Chief Robert Garcia with the Angeles National Forest. "Very rapid fire growth and very very explosive fire behavior... The days ahead are going to be very challenging."
At the height of the fire, the flames sent thick plumes of smoke thousands of feet into the air, combining with atmospheric conditions to form anvil-shaped clouds. The smoke was reported to be visible from Orange County.
The intense heat took its toll on firefighters, who had to wear heavy gear and carry equipment during temperatures that were already above 100 degrees regardless of the fire.
Seven of them were treated for heat-related injuries. They were all expected to recover.
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"The folks out there are just taking a beating," said Deputy Chief Tom Ewald, with Los Angeles County fire. "We're advocating for them to hydrate, for supervisors to pay attention to their condition."
The fire at one point caused the shutdown of the 5 Freeway in both directions, leaving thousands of drivers stuck on the road in the heat with nowhere to go as officials worked to gradually divert traffic onto surface streets.
By Thursday morning, one lane of the northbound side of the freeway was reopened, snarling drivers trying to get through the area. All southbound lanes were reopened.
By the afternoon two northbound lanes were open.
Evacuations orders had been issued for all structures on Old Ridge Route between Northlake Hills Elementary School and Templin Highway. Authorities said evacuations for Paradise Ranch Mobile Estates were lifted overnight.
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Los Angeles County has set up a website to provide emergency updates about the fire.
The cause of the blaze remained under investigation.