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.

Southampton City Council leader Royston Smith and chief executive Alistair Neill tackled Able Seaman Ryan Donovan on board HMS Astute in April 2011.
He had just shot dead Lt Cdr Ian Molyneux, 36, from Standish, Wigan.
Donovan was jailed for at least 25 years in September last year for murder and three counts of attempted murder.
Mr Smith and Mr Neill, who announced his resignation from the council on Friday, had been touring the vessel when Donovan fired six shots from an SA80 rifle in the control room.
Father-of-four Mr Molyneux tried to disarm Donovan after hearing shots on board the submarine but was shot in the head.
Mr Smith and Mr Neill later pinned Donovan to the floor until police arrived.
Mr Smith, who formerly served with the Royal Air Force, said: "It was a surreal situation to have been in."
Although he said the medal was the "best thing" he had been awarded, he added: "I wish it was for some other circumstances."
Mr Neill said: "Something of that significance never leaves you and it is right that you never forget things as extraordinary as what we experienced."
The citation for their medals, which were presented to them by the Queen at Buckingham Palace, said they placed themselves at great risk by choosing to tackle Donovan.
"By their actions they prevented further shootings and possible death or injury to others on board the submarine," it read.
Both men said their thoughts were with the family of Lt Cdr Molyneux, whose widow Gillian collected his posthumously awarded George Medal on Friday for his role in preventing a massacre on board HMS Astute on 8 April last year.
Donovan, of Dartford, Kent, admitted murdering Lt Cdr Molyneux and also admitted the attempted murders of Lt Cdr Hodge, 45, Petty Officer Christopher Brown, 36, and Chief Petty Officer David McCoy, 37.
Mr Neill will leave Southampton City Council in March 2013 to take up the same role at Herefordshire Council.
Four years of roadworks are to begin on the main road between Belfast and Londonderry road this autumn.
[NEXT_CONCEPT]
Two men who wrestled a gunman to the floor on a Royal Navy nuclear submarine have received the George Medal for bravery from the Queen.