Emergency services attended the D'Aguilar Highway at Nukku, north-west of Brisbane, before 6am on Thursday after reports the tanker and a heavy rigid transport truck were involved in a head-on smash.
Both drivers - men aged in their 30s and 50s - sustained critical injuries and were treated by paramedics, but died at the scene.
Reports have suggested the vehicles burst into "incredible flames" upon the collision.
Up to 13 fire crews attended the scene.
Three crews were still working on the scene on Thursday afternoon, with the highway expected to be closed for hours.
"Both the trucks were well-involved in flames," a Queensland Fire Department spokesman told AAP.
Police made an emergency declaration following the crash.
A 1km exclusion zone boundary has been established, encompassing the D'Aguilar Highway, the northern end of Nukku Road and southern end of Nukku Boundary Road.
"Motorists are urged to avoid the area and drive with care," police said in a statement.
Anyone with dashcam footage should contact police.
The D'Aguilar Highway links major arterial Bruce Highway near Sunshine Coast's Caboolture with the Bunya Highway in Kingaroy.
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