Police and emergency services responded to reports of collision between three trucks in Gerang Gerung this morning.
Investigators have been told the collision occurred on the Western Highway shortly after 1am this morning.
One of the trucks rolled off the road and came to rest in paddocks nearby.
The driver of the truck has been airlifted to hospital with life-threatening injuries.
A second driver has been transported by road to hospital with non-life-threatening injuries.
The third driver was taken to hospital for observations.
It is expected that the Western Highway will remain closed for some time while investigators remain on the scene.
The exact cause of the collision is yet to be established and the investigation remains ongoing.
Anyone with information is urged to contact Crime Stoppers on 1800 333 000 or submit a confidential crime report at www.crimestoppersvic.com.au