At least 100mm of rain has already been recorded in the northern Goulburn-Broken catchment and State Emergency Service officials warn those in western and central regions are also at risk of serious impact.
SES Chief Officer Operations Tim Wiebusch said on Thursday a series of watch and act alerts had been issued.
"We now have a watch and act out for major flooding on three of our river systems. The first of those is for the Campaspe River in the central part of Victoria," he told ABC News.
"Across in the northeast we've got a warning out for the Ovens and Kings rivers, which converge in and around Wangaratta and again on Saturday there may be flooding expected there."
It comes after heavy rain caused a landslide near Falls Creek on Wednesday.
The slow-moving active slip forced the closure of Bogong High Plains Road at midday, with anyone left in the area told they may not be able to leave for three days.
Only emergency and essential service workers can access Falls Creek or Bogong Village and the main road won't reopen until the threat has passed.
Most of Victoria has been warned to brace for wild weather and flash flooding on Thursday, with the worst set to hit in the afternoon and evening.
Communities near rivers, creeks and low-lying areas in the state's north are urged to stay on alert and up to date with changing warnings.
Damaging wind gusts up to 110km/h are tipped to hit alpine peaks on Thursday and clear from Friday morning.
Moderate flood warnings have been issued along the Avoca, Loddon and Murray rivers.
With large downpours expected, Premier Daniel Andrews reminded people not to drive into flood waters.
"It's dangerous for you and it's really dangerous for the person who has to come and rescue you," he told reporters on Wednesday.
Wildlife Victoria has initiated emergency response plans, anticipating an influx of calls for help.
The group doubled the number of emergency operators on shift on Wednesday night in a bid to cope.
Wildlife is particularly vulnerable in spring, with many animals caring for offspring.