A prime mover truck and car were incinerated on Tuesday afternoon when they crashed on the Great Northern Highway at Karijini, about 20km south of the Auski roadhouse.
The truck was carrying a significant quantity of ammonium nitrate, a white crystalline salt used in fertilisers and explosives.
Radiant heat from the fire prevented firefighters approaching the scene overnight.
WA Police Commissioner Col Blanch described the crash as a tragedy and confirmed authorities knew at least three people had been killed.
"Certainly it was a bit of a difficult road," Commissioner Blanch told reporters on Wednesday.
"But this is something that we consistently and constantly as police remind drivers out there to be careful.
"Pay attention and remember that every day you've got to be aware of what's going on around you."
A 2km exclusion zone was set up around the crash site and to protect the public and emergency services workers.
A Department of Fire and Emergency Services spokesperson said crews were assessing the scene on Wednesday.
"Department of Fire and Emergency Services officers and volunteer firefighters are at the scene and the State Emergency Service have been deployed to assist with welfare," they said.
Major crash detectives will attend the scene once it is safe.
It is unclear when the road will reopen.
10°C