Iron ore port and rail operations were suspended at Australia's busiest and biggest port and ships sent away, as the powerful cyclone tracks closer to the regional centre of Port Hedland.
Ilsa will cross the coast as the highest category of cyclone late on Thursday or early Friday, between De Grey and the Pardoo Roadhouse, about 100km to the northeast of the mining town.
Port Hedland mayor Peter Carter said the town of about 16,000 was expecting a "really rough night".
"It's getting closer and closer," he told AAP.
"Cat five ... that's strong winds in anyone's terms."
Bureau of Meteorology spokesman Todd Smith said category five cyclones were "incredibly dangerous".
"That is going to cause a heap of damage," he told reporters.
Mr Smith said any buildings not constructed to withstand the fierce storm would suffer extensive damage.
"Fortunately it looks like the system is going to cross in a relatively unpopulated part of the coast," he said.
Manager of the remote Pardoo roadhouse, Will Batth, said he was planning to stay and hunker down with a colleague once the storm hit.
"We haven't had any as strong as this in many years. This is a big one," he said.
"(But) there's no point in worrying. I can't stop it."
Warrawagine cattle station manager Belinda Lethbridge said the situation was concerning but her team had prepared as much as they could and it was now down to luck.
"It is what is .. We just have to wait it out now and see what happens," she said.
"It should be okay."
She said her family and staff would sit out the cyclone together and expected to be flooded in by swollen rivers after it passed.
Cyclone Ilsa, was about 155m north of Port Hedland by late afternoon.
It is expected to track inland towards the mining town of Telfer before crossing into the Northern Territory.
Department of Fire and Emergency Services Commissioner Darren Klemm said the weather system would have a significant impact on communities in the warning area.
"The strength of the cyclone will be maintained as it moves quickly inland," he said.
"All the preparation work that's gone into those remote Aboriginal communities, the mine sites and the town and the pastoral stations is really critical to make sure people are staying safe."
Evacuation centres were opened in South Hedland, Newman, Marble Bar and Nullagine.
"If your plan is to leave your residence or place of work and go to an evacuation centre, you need to do that," Mr Klemm said.
Workers and tourists at Eighty Mile Beach caravan park and nearby cattle stations have been evacuated, along with non-critical workers from mines sites across the region.
Production at Newcrest's Telfer mine slowed as the site was evacuated to all but a skeleton crew, with the cyclone expected to track inland through the area on Friday.
Communities from Bidyadanga to Port Hedland and inland to Marble Bar, have been urged to find shelter immediately.
"It is too late to leave," the warning said.
"Stay in the strongest, safest part of the building."
Abnormally high tides, flooding, destructive winds and up to 300mm of rain are forecast.
Extra emergency workers, essential supplies and aircraft have been sent to the area and Port Hedland's massive iron ore export port has been closed, with ships ordered to leave the area.
The last time a category five cyclone hit WA was Severe Tropical Cyclone Laurence, which hit a very similar stretch of coastline in December 2009.
