Five people are dead after a light plane smashed into the DFO Shopping Centre in Essendon and burst into flames.

The plane, reportedly carrying a pilot and four American tourists on a golf trip to King Island, took off and got to about 30 metres before veering left and crashing into the centre. Police suspect "catastrophic engine failure".

The pilot made two mayday calls before impact.

Two bodies have been pulled from the wreckage but there were no reports of injuries to people on the ground.

The plane was operated by the Essendon-based Corporate and Leisure Aviation.

It is unknown whether regular pilot and company owner Max Quartermain was at the controls at the time of the crash.

The company's website states that Mr Quartermain was the holder of an Air Operations Certificate for more than 38 years and had an "impeccable safety record".

​A witness, Ross Barker, told Channel 9 he saw the plane clip the centre's roof, cartwheel, and then smash through the centre's southern wall. The wreckage ended up in the centre's loading bay and caught fire.

An Ambulance Victoria spokeswoman said "we assessed some people at the scene but we haven't treated or transported anybody".

"The people that we assessed were on the ground."

Firefighters took more than 90 minutes to control the blaze before finally putting it out about 10.30am, an MFB spokeswoman said.

More than 60 firefighters have worked hard to bring the fire at DFO near #Essendon under control. Crews to remain on scene for some time pic.twitter.com/R1Y8ygSxOg

— Paul Stacchino (@MFBChief) February 20, 2017

A spokesman for the company said they were unable to make any comment until they had received confirmation from Victoria Police.

The Tullamarine freeway was closed so investigators could preserve debris that landed on the road.

#Essendon pic.twitter.com/PaJfZg7YEC

Footage from the scene showed firefighters pouring water on a large hole in the centre's roof. Other parts of the roof appear to be on fire.

#BREAKING: Reports are coming in that a plane has crashed into the DFO at Essendon, Melbourne. Live stream: https://t.co/QssKuwEgXi #9News pic.twitter.com/fzSju1Dq1G

Angelo Tsatas was on the scene and tried to help but couldn't get close enough to the raging flames.

"I heard the engine revving real loud. I saw the plane bank to the left. And then, as you know, it's hit the building and ripped off everything. I screamed out to the boys, ran over with fire extinguishers. But it was just to intense, couldn't get close enough, got about 20 metres away, but there was nothing we could do.

"The fire was higher than the building, and the heat was just too much. And everything was exploding. I think there were gas bottles, there was a car on fire."

Caller Frank told 3AW he saw the plane taking off.

"My heart's absolutely racing. I was just driving past under the Bulla Road Bridge. As I passed over the runway I saw to my right a small plane. It looked unusual, the way it was taking off did not seem right. And as I looked in my rear-vision mirror I saw a ball of flame – it looks like it's hit the DFO building.

"It was taking off to the right off the runway, it did not come over the freeway at all."

Plane crash at Essendon DFO Photo: Nine News

Debbie told 3AW she could see explosions and fire licking the side of the shopping centre.

"I'm directly opposite the crash. It's just billowing black smoke, it hit a furniture store. There are constant explosions going off, there is black smoke billowing up into the sky, there are flames leaping up the side of the building. It's terrible.

"It hit into the back of the building. Along the freeway side is a driveway for vehicles and loading docks, it's plummeted into the side of the building. There is a gaping hole in the side of the building."

Good Guys worker Ash Mayel was coming down the Tullamarine Freeway off ramp when he felt the explosion about 100 metres from the crash.

"We felt the shock wave from it," he said.

"The car has shaken. We got out and saw the fireball go up. We thought someone had set off a bomb."

As soon as Mr Mayel was told a plane had crashed into the building, he and his friends tried to get as close as they could to help.

"But the fireball that was there, there was nothing we could do, we couldn't get close to it," he said.

"It's taken off half the building. And then it dawns on you that people are inside there and what can we do? Nothing."

A colleague, who saw the plane crash, was left badly shaken.

"He's gone home, he couldn't deal with it," Mr Mayel said.

Firefighters at the scene in Essendon. Photo: Jason South

Collin Ting works at Cafe Chezzi inside the DFO food court and said he could see a lot of black smoke coming from near the airport.

"It's quite far from us, but I can see a plane has crashed near the entrance to the airport."

He said he had not yet been told to evacuate.

The Tullamarine Freeway is closed in both directions between English Street and Bell Street, and the Calder Freeway is closed in both directions between McNamara Avenue and Bell Street.

Ambulance Victoria confirmed the plane was not an air ambulance, as had earlier been reported on social media.