The state's peak motoring body, the RAA, has called on the next federal government to commit to duplicating Augusta Highway.
In the last five years alone there have been 199 injuries and 19 fatalities, prompting the group to describe the corridor as one of South Australia's most dangerous roads.
Such a project has an estimated price-tag of $2 billion and would take several years to complete.
RAA's senior manager of road safety, Charles Mountain, said such a project was a high priority given the traffic - including B-doubles and freight vehicles - that use the road as well as anticipated growth and developments in the Upper Spencer Gulf area.
"The importance of the corridor will increase," he said.
Mr Mountain also highlighted the works to duplicate the highway through Port Wakefield and an overpass north of the town as well as its crash history as part of the need for an upgrade.
"For these reasons, it's quite timely that the Augusta Highway be considered," he said.
Mr Mountain said the role the highway plays, its traffic including B-doubles and the amount of intersections were among the safety concerns for the road.
A fact sheet produced by the RAA, for federal priorities in the state, detailed some of the safety risks on the stretch of road, particularly highlighting the lack of overtaking opportunities.
"As a major strategic freight route of high national significance, Augusta Highway is ideally positioned to be at the forefront of the nation's autonomous freight innovation," the fact sheet read.
"As a matter of urgency, RAA is calling on the next federal government to commit funding for staged duplication of freight, tourist and regional traffic, and to reduce the number of people injured and killed on the road every year."
On Monday, the South Australian Chamber of Mines and Energy also joined the call for the corridor to be upgraded.
In a list of state budget priorities, SACOME said the duplication of the Augusta Highway would create economic efficiencies for the resources, agricultural and freight sectors.