The male truck driver was taken to hospital with non-life-threatening injuries.
One of the cars was left trapped under the truck.
At least 16 emergency services vehicles were at the scene.
Chief Commissioner Graham Ashton said they did not believe the driver of the Porsche was injured and he decided to flee the scene on foot. He said the Porsche had been driving at excessive speed on the freeway which caused police to pull him over and it wasn't unusual to impound a vehicle under that offence.
His identity and whereabouts is not yet known.
He said that if the driver was watching his press conference: "I strongly suggest that he get himself down to the nearest police station."
Ashton said it was believed the truck driver suffered a medical episode at the scene and after the crash.
"We don't know at this stage what caused him to drive the truck into our police members," he said.
"We just don't know."
"The truck has also made considerable contact with the Porsche.
"This is a real tragedy and so tonight will be spent notifying loved ones of our four officers.
"A very tragic night indeed we're having to respond to."
A witness told the Herald Sun the accident site was horrific.
"It was carnage," they said.
"There were civilians trying to run around and help, it was horrible."
The newspaper said about seven people and an off duty doctor and paramedic were the first on the scene to help.
Ashton said it the largest single loss of police lives in one incident in the history of Victoria Police.
"It's a very tragic night for Victoria Police and again highlights dangers that go with the every day nature of police work.
"Our thoughts are with families of officers who lost their lives tonight."
Police are expected to release more information in a press statement this morning.
Premier Daniel Andrews last night said four families' hearts were breaking.
"Our hearts are breaking with them," he said.
"We grieve alongside them – just as we grieve with every member of Victoria Police and every member of our emergency services family.
"In the coming days, formal investigations will tell us why – how – this could possibly have happened.
"But one thing is already clear – though we may not yet know their names – we will always call them heroes."
Police Minister Lisa Neville said the accident was an "unimaginable tragedy".
"I am thinking of the entire Victoria Police family who are going through a deeply distressing time right now," she said.
"My thoughts and prayers are with the family, friends and loved ones of those who have been taken from us far too soon.
"Policing is difficult and challenging work and we are reminded yet again of the bravery of all of our police officers in keeping Victorians safe.
"The Victorian Government grieves with you and we are thinking of you."
The Police Association Victoria secretary Wayne Gatt said they were "shocked and immensely saddened" by the accident.
"This is a brutally sad reminder of the danger police face in the course of their service, every minute of every shift," he said in a statement.
"We mourn their loss, we grieve with their families and colleagues and we will never forget them."
