At about 1.45am, emergency services were called to the Hume Highway near Spring Dam Road, Coolac, about 18km north of Gundagai.
They found that four trucks had collided.
A driver, who is yet to be formally identified, died at the scene.
Three other drivers were treated by paramedics and taken to hospital for mandatory testing.
The Hume Highway is closed southbound and is expected to be closed northbound between Coolac and Jugiong Hill for a number of hours.
