Emergency services were called to Oaklands Road in Oaklands Junction about 7.05am after a white Utility, a white Isuzu truck and a blue Isuzu truck were involved in a crash.
Firefighters arrived to find four people trapped inside at least three cars.
The male driver of the utility was taken to hospital with life-threatening injuries.
The male driver of the blue Isuzu was taken to hospital with serious injuries and his passenger was taken to hospital with non-life-threatening injuries.
The male driver of the white Isuzu truck was taken to hospital with non-life-threatening injuries.
Police are investigating the exact circumstances surrounding the crash.