Headingley RCMP said the fatal collision took place on Hwy 3 and Road 38 NW in the RM of Macdonald.
The car, travelling southbound, crossed the centre line of the highway and crashed head-on with the semi, said police.
The driver of the car, a 48-year-old man, was pronounced dead at the scene. The 41-year-old semi driver from Brandon was uninjured.
Police said it’s not clear at this point if alcohol or drugs were factors in the collision, but RCMP continue to investigate along with a Forensic Collision Reconstructionist.
WATCH: Truck driver collides with motorcyclist at intersection