Homes have been inundated by floodwater in Fitzroy Crossing and the Great Northern Highway cut in both directions, with some residents evacuated 400km to Broome by helicopter.
The fast-flowing waters also washed away part of a major bridge, as authorities warned the Fitzroy River would reach a record-breaking peak of 15.6 metres late on Tuesday.
"This is a dangerous and fast-changing situation," WA Emergency Services Minister Stephen Dawson told reporters.
"We have not seen rain like this for at least a hundred years so it's kind of shocking to see the water as high as it is."
Fire and Emergency Services Commissioner Darren Klemm warned residents in the communities of Willare and Noonkanbah they would be inundated in the next 24 to 48 hours.
"People need in those areas to get to higher ground," he said.
He said roads had been cut and it was too late to leave, with the region "facing at least a one-in-100-year" flood event.
The rain is coming from ex-tropical cyclone Ellie which has dumped between 200mm and 500mm since Saturday, with more widespread heavy falls forecast into the week.
The weather system is expected to move slowly west during the next 24 hours and be east of Broome, where the airport runway is already closed due to water, with more flooding and winds up to 90km/h expected.
Meanwhile, major flooding continues in the western NSW town of Menindee, with the Darling River holding steady near 10.2 metres.
The Bureau of Meteorology warns further rises to 10.7 metres are possible from Thursday, above the 1976 flood record of 10.47 metres.
"At present, 10 properties have been evacuated, while 20 other property owners have decided to shelter in place," NSW SES incident controller Gavin Arnold said.
An evacuation order remains in place for properties expected to be impacted by flooding.
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