Delivery partners Balfour Beatty, Kier and Keltbray are now waiting for the green light to start the project, which is to be delivered under an enterprise-wide collaborative working agreement.
The firms will upgrade the remaining 18 miles of single-carriageway sections and key junctions on the route between M6 Junction 40 (Penrith) and the A1 at Scotch Corner.
Archaeological work and utilities diversions are currently taking place along the A66.
Once the period for challenging the DCO expires next month, the Government will then review any need to approve the full business case for the scheme.
The A66 Northern Trans-Pennine project is one of the most critical road upgrades in the north of England and was designated by Government as a “Project Speed pathfinder” project.
Under the acceleration plan, the team had the goal of halving construction time for the project, bringing forward the opening by five years to 2029.
The scheme will involve five bypasses being built and an underpass dug at the Kemplay Bank roundabout near Penrith.
Stewart Jones, National Highways project director, said: “We are delighted to have received approval and to be able to give the people of Cumbria, County Durham and North Yorkshire some positive news.
“A lot of hard work has gone into getting us to this position. Now we can push on and deliver this project as efficiently as possible.”
National Highways first recommended improving the route in 2016. After public consultations in 2019 and 2021, a decision to proceed was initially expected last November but was pushed back to March to allow for further impact assessments.