Emergency services have answered multiple calls for help in the town of Fitzroy Crossing, which is now surrounded by rising floodwater as ex-tropical cyclone Ellie continues to dump heavy rain.
Some hospital patients have been evacuated to Broome and the Great Northern Highway is cut in both directions, with Fitzroy River expected to peak at a record 15.6 metres late on Tuesday.
"This is a dangerous and fast-changing situation," WA Emergency Services Minister Stephen Dawson told reporters on Tuesday.
"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.
"This is an incredibly serious situation. Roads have been cut off and it is too late to leave."
He said the only way in and out was by helicopter and the region was "facing at least a one-in-100-year" flood event.
The fast-flowing floodwaters also washed away part of the new Fitzroy Bridge, with authorities saying it could be many weeks before the Great Northern Highway, a major transport route, reopens.
"There could be significant damage to a couple of piers in the mid-spans but we won't be able to ascertain the level of damage until the floodwaters drop," said WA Main Roads operations director Peter Sewell.
He said the department was also monitoring the bridge in Willare, which is three times the size with a similar construction.
An emergency flood declaration has been issued for the Broome and Derby-West Kimberley shires with major flooding also expected to impact Willare, Noonkanbah, Mount Barnett and Christmas Creek on Wednesday and Thursday.
The weather system is expected to move slowly west during the next 48 hours and be east of Broome, where the airport runway is already closed due to water and more flooding, with winds up 90km/h expected.
The system has dumped between 200mm and 500mm of rain since Saturday, with Dimond Gorge recording 350mm in one day and further widespread heavy falls forecast for the next few days.
Earlier, Fitzroy River Lodge scrambled to evacuate guests as the rising flood waters swamped the hotel's grounds.
The lodge's manager Kandula Herat said initial plans to fly them out using a helicopter was abandoned after the proposed landing pad went under.
"There was no place to land the chopper. The new bridge is pretty much washed away and the water was up to 15 metres," he said.
Authorities eventually found a boat large enough to transport the hotel's 15 European and Australian guests across the swollen river.
They made it across about 1.30pm and were later flown by helicopter from the Fitzroy Crossing evacuation centre to safety in Broome, 400km away.
Mr Herat said the lodge's 18 staff remained on site and were safe for now despite the river rising more than a metre higher than the 2002 record peak of 13.95 metres.
"The river is still rising and will possibly peak tomorrow," he said.
"Another metre and a half and it's going to be inside the rooms. Every hour the situation is changing."
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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