Flames were seen spreading through the trailer on the side of the northbound lanes after it caught fire about 5am.
Rural Fire Service Superintendent Patrick Westwood said it took six fire trucks and about 25 firefighters to put out the blaze.
He told the Border Mail, a blown tyre may have contributed to causing the fire.
“It started a small grass fire next to the truck as well, but both were controlled and in hand by 6am,” he said
“I do believe the trailer had postage items in it … there was very little salvageable.”
The driver pulled over and tried to put out the fire, but it quickly became “far too dangerous”, and the trailer was destroyed, the mail service said in a statement.
“Fortunately and most importantly, nobody was hurt,” it read.
The driver managed to disconnect the trailer from his prime mover and was cleared of any injuries after being examined by paramedics.
Authorities created a makeshift lane to allow traffic to continue at a slowed speed until the truck was recovered about 10.50am.
It comes after another Australia Post truck was destroyed by fire on the same highway in April last year.
It took four Rural Fire Service trucks to extinguish the blaze at the time, which resulted in a large amount of letters being destroyed that were on their way from Sydney to Melbourne.
Australia Post said it would start sorting through the parcels damaged in the latest fire when it is safe to do so, and would use machine scanning data to help contact the senders.
Customers who posted parcels in Victoria on Wednesday 7 or Thursday 8 September for New South Wales or Queensland are advised to contact Australia Post on 13 13 18 from Monday for further information. Australia Post issued an apology to affected customers.