Sunday will be the hottest in the north-west with temperatures predicted to soar to around 44 degrees Celsius in Mildura, six hours north-west of Melbourne, as the heat begins to build.
A mass of hot air is being strengthened by a cyclone brewing off the West Australian coast.
"Monday will be the warmest day for much of Victoria including the Melbourne area," said Diana Eadie, from the Bureau of Meteorology.
"We're expecting the temperature to be around 41 or 42 degrees.
"We are going to see a large part of the state exceeding 40 degrees for the first time for many of those areas since January of last year."
The overnight temperature will make the conditions particularly dangerous.
Overnight Sunday and into Monday the temperature won't drop below 24 degrees, meaning people won't have a chance to recover between the hot days.
"This is more than just one hot day - it could potentially be very dangerous for people's health," Eadie said
"Generally speaking, it has been quite a mild summer thus far and that's why this particularly hot day is really going to take people by surprise."
Extreme heat kills more Australians each year than any natural disaster.
A gusty cool change is expected in the latter part of Monday, leading to an elevated fire risk.
The fire danger in the north will be severe, authorities say.
The heatwave is also expected to hit Adelaide and Sydney with temperatures ranging between the high 30s and low 40s.