Ilsa is expected to be the first category-four system to strike the region in almost a decade when it hits the coast near Port Hedland in coming days.
Mayor Peter Carter said there had been a building boom in recent years and many structures had not endured a cyclone of Ilsa's projected strength.
The cyclone will test the town's infrastructure and new homes, he said, but building codes stipulated cyclone-strength construction so they should be OK.
"We're watching it very closely. Everyone is on alert here," Mr Carter told AAP on Wednesday.
"It is a category-four cyclone ... and we know what happened with Cyclone Tracy in Darwin."
Ilsa is currently a category-three cyclone, about 500km north of the town that's home to Australia's largest bulk export port, used by companies such as BHP and Fortescue Metals Group to load iron ore onto ships.
The massive weather system is expected to strengthen before crossing the coast near Eighty Mile Beach, about 330km northeast of Port Hedland, late on Thursday or early on Friday, with gusts up to 270km/h forecast.
An alert has been issued for Bidyadanga to De Grey in the Kimberley and Pilbara regions, as authorities urge residents to make final preparations.
Heavy rainfall, destructive winds and abnormally high tides are forecast as Ilsa moves southwest and turns towards the Pilbara coast.
Communities from Broome to Marble Bar and Whim Creek have been warned to be ready for cyclonic weather.
Mr Carter said Port Hedland, a town of about 16,000 residents and fly-in fly-out workers, had been working hard to prepare for Ilsa's arrival.
"Being a transient town we're trying to get people who haven't been through a cyclone to put their barbecues away, their outdoor furniture and their wheelie bins away because those things can become missiles when you get over 200km/h winds," he said.
Workers and tourists at Wallal Downs cattle station and Eighty Mile Beach caravan park are being evacuated, along with non-critical workers at Newcrest's Telfer mine and BHP's sites across the region.
Extra emergency workers, essential supplies and aircraft have been sent to the area as authorities warn the North West Coastal Highway could close between Port Hedland and Broome due to flooding.
The Port Hedland port is being cleared of vessels including iron ore carriers.
The last severe cyclone to impact the coast near Port Hedland was Christine, which crossed the coast as a category-four system in December 2013.
Cyclone Tracy, rated category four, devastated Darwin in the early hours of Christmas Day 1974, killing more than 70 people.
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