Jim Madden, 81, and wife Carmel, 80, were at home in Tower Hill in Victoria's south west when the truck veered off the Princes Highway and crashed into their property just after 7am on Friday.
Footage from the scene shows the truck crashed through a paddock, into a fence and down one side of the house before collecting part of the roof.
The elderly victims of the truck crash were well-known farmers in the area. (HANDOUT/Nine News)
The truck driver, a 70-year-old Portland man, suffered non-life threatening injuries and was taken to hospital for treatment.
Detective Sergeant Stephen Hill said the cause of the crash was under investigation.
"We're keeping an open mind as to what was going on," he told reporters at the scene on Friday.
"Whether it's a mechanical fault with the truck, whether there's a medical episode involved, whether it's inattention, whether it's phone use involved, all those things will have to be looked at in the next few days."
The small town of Tower Hill is near Warrnambool in the south west of Victoria. (HANDOUT/Nine News)
He described the section of the road as "dead straight" and said there would be no reason for vehicles to swerve unless they were overtaking.
Local business owner Richard Crawley said the victims were farmers with many family connections to the area and he expected the crash to affect the community.
"It will have a big impact, Jim and Carmel Madden were very well-known people," Mr Crawley told AAP.
About 100 people live in the Tower Hill area, according to the 2021 census.
The truck hit a section of the house's roof after crashing through a fence. (HANDOUT/Nine News)
Mr Crawley said he drove near the house in the hours after the crash, before he was diverted away.
"It's sort of hard to fathom what actually has happened, because it doesn't make any sense at all that a bloody great big B-double truck on a dead straight part of the highway can do what it did," he said.
Detectives from the Major Collision Unit have travelled about three hours from Melbourne to the scene to investigate.
Anyone with information about what happened or relevant footage is urged to contact police.