The man is in a critical condition following the Friday morning crash, but his truck still dangles precariously from the Bolte Bridge, part of the busy CityLink tollway
The road's inbound lanes have been closed, causing major delays.
MFB Assistant Chief Officer Adam Dalrymple said it appeared the truck driver had swerved to avoid a car that had suddenly veered in front of him.
'From all reports the car veered across and the truck took some evasive action and that's how the incident began,' he told reporters at the scene.
Police say the truck had collided with a car on the bridge shortly after 6.30am (AEST).
The driver of the truck, believed to be aged in his 30s, was ejected from the cabin and fell on to Mark Street, which runs below the bridge.
The man was found by a nearby factory worker, who comforted him until an ambulance arrived.
'I just made sure he was conscious and kept him calm until paramedics were able to take over,' he told the Seven Network.
The driver had suffered serious head and pelvic injuries, an Ambulance Victoria spokeswoman said.
He remains in a critical condition at the Royal Melbourne Hospital.
The other driver, a man believed to be in his 20s, suffered minor injuries and is in stable condition in hospital.
Cranes have been brought in to secure the dangling truck and to safely remove it later on Friday.
The crash also cracked a brick wall on a building beneath the bridge.
Fire crews are examining the building to make sure the damage doesn't cause it to collapse.
A CityLink spokeswoman said all inbound lanes were closed at Flemington Road and heavy traffic delays were continuing.