On Saturday a man in his 40s was killed in a crash at Keilor Downs.
In the early hours of Sunday morning a woman in her 30s was killed and a boy of primary school age transported to hospital after an accident in Highton.
Just before 1.30pm on Sunday an accident involving a single car on the Hume Freeway at Glenrowan claimed the life of a man believed to be in his 40s.
The car was on fire when firefighters from Glenrowan brigade arrived on scene. South Wangaratta brigade also responded to the crash.
CFA volunteer Mick Daws posted on Twitter: "Just back from another car accident on the Hume Freeway, another life lost tragically. Impacts the lives of the emergency services as well."
Another multi-vehicle crash happened just after 4pm on the Maroondah Highway at Donaldson Lane near Bonnie Doon.
A man and a woman died at the scene and a woman in her 50s was airlifted to the Royal Melbourne Hospital.
Firefighters from Bonnie Doon, Maindample and Merton were involved in the response.
More information about all the weekend crashes is available on the Victoria Police News website.