The blaze, which started just before 4pm, consumed a car wrecking yard on Fitzpatrick Street and spread to two adjoining buildings, a factory and a gym, Fire and Rescue NSW said.

Within one minute of crews arriving, they were confronted with "huge flames" and "multiple explosions" and radioed for reinforcements.

Two men sustained serious burns to their faces in the blaze; one was also burnt on his arms. Both were taken to Royal North Shore Hospital in a serious condition with a police escort.

It is understood the pair were carrying a gas cylinder when it exploded in their faces. A witness told Nine News she saw one of the men run out of the business naked, his clothes burnt away.

"The other man started to scream, 'Call two ambulance,' " the witness said.

Ambulance crews, including special operations team paramedics, remained at the scene in case there were any further patients. Police earlier evacuated people from nearby businesses.

Superintendent Krimmer said about 100 firefighters from 20 surrounding stations were working on the fire, which was expected to burn for several hours.

"The fire still continues to burn in a number of wrecked vehicles, with a large amount of fuel, spoils, petrol and tyres that have fuelled the fire," he said.

"The cause of the fire is not known at this stage."

REVESBY | UPDATE: 100+ #FRNSW f/fighters at a car wrecking yard #fire. Fire in crushed cars & adj. factory. pic.twitter.com/7yE8iaS7hH— Fire & Rescue NSW (@FRNSW) May 25, 2016

Thick black smoke from the blaze blanketed the area, including the nearby M5 motorway.

As firefighters worked, surrounding streets were closed and traffic in others slowed. Afternoon buses in Revesby and Milperra were delayed by up to 25 minutes.

The NSW Environment Protection Authority was also on the scene.

Andrew Millett, who was flying the Seven News helicopter above the scene, said firefighters had a "very hard time" getting on top of the fire, which had "intense" flames.

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