Tropical Cyclone Mitchell is expected to intensify into a severe category three system as it tracks just north of Karratha on Saturday night, bringing with it heavy rain, severe flash flooding, and destructive winds.
Residents from Whim Creek to Mardie including the mining town of Karratha are under an emergency warning and have been told to shelter indoors immediately.
The warning states there is a threat to lives and homes and it is too late for residents to leave.
They are being told to take shelter indoors, staying in the strongest part of the building and away from doors and windows.
Very destructive gusts of up to 220 km/h are possible on the Pilbara coast around Karratha, Dampier and Wickham overnight, and in Onslow on Sunday, according to the Bureau of Meteorology.
"Damaging to destructive winds are expected to ramp up in the next 24 hours, many places will see their strongest winds kick in late Saturday," said bureau forecaster Angus Hines.
"Those winds are strong enough to bring down big branches or entire trees, damage property, and lead to power outages."
An evacuation centre has been set up at Karratha Leisureplex, and a second evacuation centre is being opened further south at the Onslow Multi Purpose Centre.
The cyclone was offshore about 165 kilometres northeast of Karratha and 150 km from Port Hedland late on Saturday afternoon.
Mitchell is expected to make landfall near Onslow on Sunday afternoon.
Warnings are in place for many communities including Port Hedland, Karratha, Onslow and Exmouth.
Residents south of Mardie towards the town of Onslow have been told to get ready to take shelter.
The ports of Ashburton, Cape Preston West, Dampier, Port Hedland and Varanus Island are closed as the weather system approaches.
Authorities warn the central and west Pilbara coast faces the risk of flash flooding throughout the weekend, with the west Gascoyne region likely also affected by Monday.
Abnormally high tides will also present a serious flood risk for the Karratha region in the early hours of Sunday and towards Onslow Sunday afternoon, the bureau says.
The cyclone's impending arrival comes as other outback towns are still feeling the brunt of major flooding.
In the Northern Territory, more than 400 people bussed 230km to Darwin from Daly River on Wednesday may have to wait days before they can return, as riverine flooding is not expected to peak until early next week.