Emergency authorities have ordered residents in Charlton and Echuca to leave their homes immediately, where up to 400 properties could be affected.
Residents in Shepparton, Orrvale, Murchison and Mooroopna have been told it is too late to leave and they should find shelter in the highest location possible.
Victorian State Emergency Service says more than 7300 homes and businesses in the Shepparton area could be affected by the rising waters.
There were 127 flood rescues in the past 24 hours, with the majority in the Shepparton area, the SES says.
Prime Minister Anthony Albanese has flown into Bendigo to tour the flood-affected areas with Premier Daniel Andrews.
"This is a very severe weather event that's having an impact in urban communities but also in regional communities right throughout Victoria, but particularly there in the north and the northwest," Mr Albanese told ABC Radio on Sunday.
"We'll be working with the Andrews government to make sure that people get the support that they need at this difficult time."
Australian Defence Force personnel are helping authorities evacuate residents, and an evacuation centre will be opened in Mickleham at a Commonwealth facility.
Shepparton has been hit by major flooding, with the swollen Goulburn River expected to continue to rise through Sunday before peaking at 12.2 metres early on Monday.
That was higher than the 1974 flood level of 12.09 metres, the Bureau of Meteorology said.
Television footage shows buildings in the middle of town surrounded by a vast inland sea of brown water, and residents using sandbags in a bid to stop it.
Major flooding has peaked at Murchison, where the Goulburn peaked at 12m.
Major flooding has also hit communities along the Avoca River to Charlton, where the rising waterway had swollen to 7.73m on Sunday morning.
The river at Charlton could peak at 8m early on Monday.
The Wimmera River is also flooding with residents in Horsham warned major flooding was possible early on Monday.
Echuca is expected to be hit by two flood peaks, including one by Tuesday and another later in the week.
Authorities predicted about 200 Echuca homes would be affected by floodwaters.
Residents were advised to prepare to be away from home for seven to 10 days, with Echuca Village expected to be impacted by the middle of next week, with flow-on effects from the Goulburn and Murray rivers.
The Midland Highway, also known as the Mooroopna Causeway, was slated to close on Sunday afternoon but closed on Saturday evening between Mooroopna and Shepparton.
About 6000 building are without power.