More than $18 million will be spent installing continuous safety barriers and widening the Midland Hwy between Cosgrove South and Benalla.
The project is part of a $157.57 million funding boost from the Australian and Victorian governments to improve road safety.
The funding will support a further 54 road safety projects across the state, including 30 projects in metropolitan Melbourne to make intersections safer and a further 24 projects in regional Victoria.
The upgrades are jointly funded under the Road Safety Program, with the Federal Government contributing $112.46 million and the Victorian Government providing $45.11 million.
Deputy Prime Minister Barnaby Joyce said the road upgrades would help keep motorists safe and the economy strong.
“One life lost on Australian roads is one too many, which is why we are delivering this funding to improve roads right across the nation,” he said.
“We are investing in shovel-ready projects that can get under way quickly, saving lives sooner while supporting local construction jobs, businesses and the economy.”
Victorian Roads and Road Safety Minister Ben Carroll said better and safer road infrastructure would drive down road trauma.