RCMP say the head-on crash happened on an untwinned part of Highway 63 near the community of Wandering River.
Police say the driver of the pickup was pronounced dead on scene while the driver of the transport truck was being treated in hospital for serious but non life-threatening injuries.
The highway was closed Tuesday morning in both directions as officers investigate.
Last year the Alberta government promised that Highway 63 — known as "Death Highway'' for the high number of fatal collisions over the years — will be twinned by the fall of 2016.
The highway is the main road to the busy Fort McMurray oilsands region.
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