Authorities are confident the Calder Freeway will reopen in time for Wednesday's morning peak, almost 24 hours after a horror smash that claimed the life of a 49-year-old Ascot Vale man.

Three cranes and a heavy haulage truck were brought in to "upright" a petrol tanker that had flipped on its side near Milleara Road in Keilor Park.

Police believe the driver swerved to avoid a car that pulled out in front of the truck in the centre lane of the freeway.

The resulting crash, described as one of Melbourne's worst, involved seven vehicles, with the truck colliding with a number of other cars.

Video taken by a passerby shortly after incident shows a line of battered cars leading up to the crushed white Toyota that was carrying the deceased man.

The crash is being probed by the Major Collision Investigation Unit, but as of late on Tuesday night police were not able to say if investigators expected to find more bodies in the wreckage of the Toyota or if anyone had been interviewed.

Motorists faced lengthy delays throughout Tuesday, as the Calder Freeway was closed between the Tullamarine Freeway and the Western Ring Road.

Motorists faced major delays on the Calder Freeway on Tuesday night. Photo: Pat Scala

For about nine hours the Metropolitan Fire Brigade set up an exclusion zone around the crash site as they worked to clean up a major fuel spill. The tanker was carrying 60,000 litres of fuel, a third of which leaked onto the highway.

Some of this fuel and chemical foam may have entered the nearby Steele Creek. Visitors are advised to avoid the waterway until further notice.

Late on Tuesday night, VicRoads spokesman Nerryl Kingston said he thought both lanes of the Calder Freeway would be open by the morning peak on Wednesday– or at least at a reduced speed.

However Mr Kingston said it was still a matter of "wait and see", as there was a possibility the fuel had damaged some of the road, particularly the emergency lane.

He said if authorities were not able to reopen the freeway "it's going to be congested in that area during peak hour".

"That area will become extremely heavy, like on Tuesday morning when there were significant delays that everyone was worried about".

Those looking to avoid the area should take these alternative roads:

• Inbound from Bendigo: Calder Fwy, Keilor Park Dve, Sharps Rd, Melrose Dve, Tullamarine Freeway
• Outbound from Melbourne: Tullamarine Fwy, Melrose Dve, Sharps Rd, Keilor Park Dve, Calder Fwy

The crash scene on Tuesday. Photo: Eddie Jim

After the crash, six people were taken to hospital, including the truck driver.

A woman aged in her 40s suffered neck, shoulder and arm injuries when her car overturned. She was taken to the Royal Melbourne Hospital in a stable condition.

The truck driver was also taken to the Royal Melbourne Hospital with leg injuries.

Two women - aged in their 20s and 40s - suffered neck and hand injuries and were taken to Sunshine Hospital in a stable condition.

A woman in her 60s with a wrist injury was taken to Western Hospital Footscray, while a teenage boy was taken to Sunshine Hospital as a precaution.