Emergency services say it is a miracle that six truck drivers have walked away unhurt from a fiery multi-truck crash without injuries.

Police believe two trucks collided while travelling northbound along the Hume Hwy in Breadalbane, about 32km southwest of Goulburn, about 5am on Tuesday.

WATCH THE VIDEO ABOVE: Fiery seven-truck crash closes Hume Highway

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Both vehicles then smashed into four more trucks parked at the Windmills Rest Area which sparked a major inferno.

“Explosions” were reported as the blaze tore through the “flammable contents within the vehicles” and destroyed all seven trucks.

“One truck was carrying eight tonnes of butane cans, another was transporting resin, a third contained memory foam and a fourth was packed with alcohol, fuelling the resulting fire and explosions,” Fire and Rescue NSW said.

The drivers are all lucky to be alive after the Hume Highway crash. Credit: 7NEWS

Paramedics arrived soon after and treated six male drivers for minor injuries, two of which have also been taken to hospital for mandatory testing.

Earlier, police had suspected that a seventh truck was involved and held fears for that driver’s safety.

They have since clarified only six vehicles were involved. 

A 300m exclusion zone was in place around the crash site, which closed the highway in both directions as about 40 firefighters raced to the scene.

Southbound lanes on the Hume Highway reopened to traffic on Tuesday afternoon. The northern side remains closed, with vehicles being diverted through Canberra. 

The blaze was eventually extinguished but could still be seen smoldering about midday, raising concerns for locals.

Fire Rescue NSW Chief Superintendent Stephen Hirst told 7NEWS the smoke is believed to “contain formaldehyde”.

The Hume Hwy has been shut in both directions after a truck smashed into three cars and caught alight. Credit: NSW Rural Fire Service

Even limited exposure to formaldehyde can cause burning sensations in the eyes, nose, throat and lungs or even allergic reactions.

Prolonged exposure, however, can be fatal as is causes throat spasms or fluid building up in the lungs.

“We’re working diligently within that smoke, decontaminating ourselves and out equipment as we go,” Hirst said.

Firefighters are using drones to monitor the atmosphere at the crash site for harmful chemicals, with smoke still rising from the wreckages.

Motorists were urged to instead use the Federal and Barton Hwys through Canberra, a detour that took 80 minutes of extra travel time.