The blaze in California's Shasta-Trinity National Forest was burning out of control after chewing through 58 square miles (150 square kilometers) of timber and brush since Wednesday.
Aircraft were temporarily prevented from making water and retardant drops because heavy smoke was trapped under cloud cover, making for limited visibility for pilots. Firefighters working in rugged terrain were contending with hot temperatures and gusty winds.
Authorities announced Friday that a 45-mile (72-kilometer) section of Interstate 5 north of Redding would remain closed at least until Sunday.
The fire has destroyed thousands of trees — some 70 feet (20 meters) tall — that could fall onto the highway that traverses the entire West Coast from Mexico to Canada and serves as a main artery for commerce.
Truckers and other motorists were forced to take circuitous local routes that added hours to travel times.
Interstate 5 became a ghost road after fire turned hills on either side into walls of flame. Drivers fled in terror and several big-rigs burned.
Nearly 300 homes were considered threatened, but the blaze was not burning near any large towns, fire spokesman Brandon Vacarro said.
Meanwhile crews near California's border with Nevada gained minimal containment of another wildfire that closed highways on the edge of the Sierra Nevada.
A previous fire this year near Redding and another in the Mendocino area — the two largest blazes in the state this year — destroyed or damaged 8,800 homes and 329 businesses.
The Mendocino fire was expected to be fully contained by Sunday, more than six weeks after it started.