It will cover a 14.7km (nine-mile) stretch of the A6 from Randalstown in County Antrim and Castledawson in County Londonderry, either side of the Toome bypass.
Upgrading the stretches of road to dual carriageways is expected to cost Â£160m.
Infrastructure Minister Chris Hazzard said the work would "strengthen the links between Belfast and Derry".
He added that it would help to address an "infrastructure deficit" west of the River Bann.
The route will replace the existing road from Castledawson to the M22 motorway to Belfast, which sees lengthy tailbacks during peak hours on a daily basis.
"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," he added.
"I am determined to contribute towards economy growth in a regionally-balanced way, and I believe it is vital that infrastructure projects such as this are prioritised."
On occasions during the morning rush-hour on the current route, traffic grinds to a complete standstill, resulting in traffic jams stretching for miles.
The scenario is reversed during evening rush-hour as commuters return to the north-west from the direction of the M22 motorway.
Earlier this year, Northern Ireland's roads authority said the proposed route would affect about 120 landowners.
The Department for Infrastructure said ground investigation work has begun and archaeological investigations along the route will start this week.
Construction is expected to begin in October.
Mr Hazzard added the project was "welcome news" for the construction industry.
Four years of roadworks are to begin on the main road between Belfast and Londonderry road this autumn.