Police believe a truck was travelling west along the Rosedale-Longford Road, near Kellies Road, and the car the man was driving in an easterly direction collided head-on just before 6.30am.
The Toongabbie man died at the scene.
The driver of the truck was conveyed to Sale hospital with non life-threatening injuries.
Rosedale-Longford Road remains closed in both directions and local diversions have been put in place.
Investigators are appealing for witnesses and anyone with information is urged to phone Crime Stoppers on 1800 333 000 or visit www.crimestoppers.com.au