A Police spokesman said a road train and the family were both travelling on the Great Northern Highway as a third vehicle was heading in the opposite direction about 150km south of Port Hedland after 3pm on Friday.
The spokesman said the parents died as a result of their injuries.
The two children were taken to hospital but it is understood were not injured in the crash.
A GoFundMe campaign set up by Narelle Johnson described the couple as active community members who would have done anything to support the town.
The page has raised nearly $10,000 overnight. A second page has also racked up about $4,000 for the two children.
Anyone wanting to donate can visit https://www.gofundme.com/help-support-larissa-and-jack.
The road remains closed in both directions as major crash investigators arrive on scene.
Anyone with information is asked to call Crime Stoppers on 1800 333 000 or report the information online at www.crimestopperswa.com.au.
TWO Tom Price teenagers have lost their parents after they were killed in a horror crash on the Great Northern Highway last weekend.