The burned-out car was found on Sunday morning to the side of Mansfield-Woods Point Rd in Piries, southeast of Mansfield.
Police believe the car was travelling north when it lost control and hit an embankment before spinning out, ramming into a tree and bursting into flames.
All occupants died at the scene but police are yet to establish how many people were inside the car and if they were killed in the crash or resulting fire.
Disaster victim identification specialists are expected to provide an update by Monday morning.
"We think there are four," Road Policing Command Assistant Commissioner Glenn Weir told reporters on Sunday.
"We don't think there are more than four but again (it's) a really catastrophic and confronting scene."
The cause of the crash is unknown but Assistant Commissioner Weir noted it was high high-traffic area for kangaroos and deer.
Speed was cited as another potential factor, given the limit along the road is 100km/h.
It is believed the victims were colleagues, with the car rented from a west Gippsland-based company.
"All the people we think were known to each other and had a common connection through work," Assistant Commissioner Weir said.
"We think the people are relatively local within the sort of Shepparton, Benalla and Mansfield area."
Detectives are investigating a fatal car crash on Mansfield-Woods Point Road, Piries near Mansfield around 7am this morning. — Victoria Police (@VictoriaPolice) All occupants inside the vehicle died at the scene.Anyone with information is urged to contact Crime Stoppers on 1800 333 000. https://t.co/VGEoKtEtfaNovember 12, 2023
A member of the public noticed a fire on the side of the road in some trees and shrubs and stopped to find the wreckage.
They called police at 7.45am but the car, believed to be a KIA people-mover, was barely ablaze by the time officers and firefighters arrived.
Assistant Commissioner Weir said police believe the crash and the subsequent fire took place on Sunday morning, not long before the witness spotted the car.
"It's not a heavily trafficked road ... so in the pitch dark a fire would have been visible for some distance," he said.
Benign weather conditions limited the spread of the blaze.
Another two people were killed on Sunday afternoon after their small silver hatchback lost control and crashed with a truck and ute along the Midland Highway in Goornong near Bendigo.
The incidents came after 12 people died in crashes in Victoria last weekend, including five when a car ploughed into a Daylesford pub's beer garden.
More than 250 lives have been lost on the state's roads this year, surpassing its 2022 full-year road toll of 241.
23°C