At least three years of roadworks are to begin this autumn on the Belfast to Londonderry road.
It will involve a near 15-kilometre (nine-mile) stretch of new dual carriageway between Randalstown and Castledawson in counties Londonderry and Antrim.
The development will cost around £160 million and will strengthen links between Northern Ireland's two major cities, infrastructure minister Chris Hazzard said.
"My commitment to this area in delivering this £160 million flagship investment will strengthen the links between Belfast and Derry and positively develop the A6 as a key transport route into the wider North West area.
"Road users and the local community will directly benefit from this new all-purpose dual carriageway as it will reduce journey times and improve road safety."
His special adviser, Conor Heaney, tweeted that the new stretch of road on the A6 should be ready by 2019.
It replaces a single carriageway close to the M22 motorway which has been plagued by delays at busy times. Around 18,000 vehicles use the route every day.
Mr Hazzard said advanced ground investigation work had begun and archaeological excavation was due to begin soon.