The Country Fire Authority (CFA) said five carriages derailed near Wallan station, 45 kilometres north of Melbourne, on the North East line about 8pm on Thursday.
Emergency services are on their way to the scene and the rail lines between Melbourne and Sydney have been closed.
At least three helicopters have been deployed to a scene CFA described as “very chaotic at this stage”.
All passengers who were able to walk from the train have been taken to the Wallan McDonald’s and BP Truckstore area, which being used as a triage centre.
Two commuters are unaccounted for.
More to come.