Th truck and train collided at a level crossing on the Camperdown-Lismore Road near Lismore, 170 km south-west of Melbourne, occurred about 7.30am (AEST) today.
A spokeswoman for rail freight company Pacific National said the truck hit the side of the train and derailed two locomotives and 44 goods wagons.
The company and the Australian Transport Safety Bureau are investigating, the spokeswoman said.
A Victoria Police spokeswoman said the wreckage of the semitrailer's cabin remained wedged under the train.
"It could possibly take days to retrieve the body," she said.
The train driver and his observer were not injured, and the driver phoned Colac police to alert them to the accident shortly before 7.30am (AEST), the spokeswoman said.
"The scene is currently being preserved until detectives arrive and diversions will be put in place to direct traffic around the scene for several hours," she said.
The rail line is a major freight route between Melbourne and Adelaide.
Police say the crossing has give way signs but no lights, bells or boom gates.
The accident is the second on an uncontrolled rural level crossing in a month.
Two train passengers died and dozens, including the train driver, were injured when their VLocity train struck a truck on a crossing at Trawalla, near Ararat in western Victoria on April 28.
The Pacific National spokeswoman said the train driver and observer in today's crash were receiving trauma counselling.
"This is a significant derailment for Pacific National with two locomotives and 44 wagons coming off the track," she said.
"The Pacific National train was travelling from Adelaide to Melbourne on the interstate track.
"The Australian Transport and Safety Bureau is conducting an independent investigation.
"Pacific National attended the scene immediately and will conduct a thorough investigation into the incident.
