The Highways England scheme includes resurfacing around 4 miles of the westbound carriageway from Smallways to Greta Bridge, as well as repairing some of the signs.
Work will start on Monday 7 September and is due to be completed by Friday 23 October.
A contraflow system will be in place, with the westbound carriageway closed to traffic. Vehicles will run in both directions on the eastbound carriageway and there will be a temporary 40mph speed limit.
Highways England project manager Derek Dobinson said:
When complete, this project will provide drivers with safer and smoother journeys along the stretch of the A66 in County Durham.
Every effort is being made to ensure disruption to traffic and residents is kept to a minimum, and we’ll be using a contraflow system on the eastbound carriageway to keep vehicles running in both directions on the dual carriageway.
The resurfacing work will be carried out in two phases. Phase 1 will start at Smallways to Thorpe Farm Centre between Monday 7 September and Monday 12 October.
Phase 2 will be from Thorpe Farm Centre to the end of the dual carriageway to the west of Greta Bridge. This work will be carried out from Monday 12 October to Friday 23 October. These dates may change depending on the weather conditions.
The diversion routes for side roads affected by the contraflow system will be via Newsham, Barningham, Scotch Corner and ‘the snow gates’ to the west of Bowes.
Members of the public should contact the Highways England customer contact centre on 0300 123 5000.
Journalists should contact the Highways England press office on 0844 693 1448 and use the menu to speak to the most appropriate press officer.