Conditions in the town are expected to worsen during Tuesday and Wednesday.
Very destructive winds with gusts of more than 165km/h are likely to develop on the coast between Whim Creek and Pardoo on Wednesday as Rusty approaches the coast, the weather bureau says.
During Tuesday and Wednesday, very heavy rainfall is likely to lead to major flooding in the De Grey catchment.
Significant flooding is expected in the Fortescue catchment and in Pilbara coastal streams.
The cyclone's intensity, size and slow movement is also likely to lead to a very dangerous storm tide.
Shops in Port Hedland are being sandbagged, with supermarket shelves clear of water and tinned food.
Bottle shops are reporting long queues as locals prepare for Rusty's arrival.
Port Hedland's airport was shut at 9pm (WST) on Monday and all commercial flights cancelled.
The port is also in shutdown, possibly for the rest of the week at least.
Eleven schools have been closed.
Images from NASA's Terra satellite show Rusty is developing an eye 20 nautical miles wide.
The Kimberley town of Broome has been given the all-clear, however.
A second potential cyclone is developing to the southeast of the Cocos Islands and will be named Sandra if it becomes a cyclone.
- AAP