A "colossal" amount of water is moving towards the Russian city of Kurgan, the region's governor has said.
Vadim Shumkov said that the swollen Tobol river and its tributaries had produced water levels twice those of the last major flood in 1994.
Floods over the past two weeks have forced evacuations of tens of thousands of people from northern Kazakhstan and bordering areas of Russia.
They are caused by the rapid melting of snow and ice combined with heavy rain.
On his Telegram channel, Mr Shumkov urged everyone in areas threatened by flooding to leave their houses immediately, with waters expected to rise as high as 11m (36ft) above normal.
"This isn't just a flood, it's a genuine threat!" he said.
"Therefore, take children, elderly people, relatives with limited mobility and neighbours to a temporary shelter or to friends and acquaintances. Collect documents and valuables."
Kurgan - a city with more than 300,000 inhabitants - is the location of the military factory Kurganmashzavod, whose production includes infantry fighting vehicles and light tanks. There has been speculation by foreign defence media that it may at some point be in the flood zone.
People in the town of Ishim further east have also been asked to evacuate because of high levels of the river of the same name.
Petropavl in northern Kazakhstan has also been badly affected by flooding of the river Ishim. A number of rivers flow back and forth between the two countries.
Elena Kurzayeva, a 67-year-old Petropavl pensioner, told AFP on Sunday: "I was taken out yesterday and within 15 minutes, the water had come in."
Water levels in both the Ishim and the Tobol, which form part of the world's seventh longest Ob river system, are not expected to peak until 23 or 24 April.
Focus has shifted to the two rivers after flooding in the Ural river basin devastated a swathe of Russian and Kazakh territory further west last week.
The flooding is being described as the worst to hit the region in 80 years.
In the city of Orenburg, houses in some areas were left almost completely submerged.
A week earlier, the city of Orsk was badly affected after a dam burst and saw rare public protests over how officials handled the floods.
Russian Emergencies Minister Alexander Kurenkov, who is visiting the area, has assured Orsk residents they will be compensated.