The Bolton Road End junction to Crackenthorpe project involves reconstructing and resurfacing the single carriageway section of the route west of Appleby.
Several other projects are also taking place at the same time to minimise future disruption to road users, including drainage and kerb repairs and the replacement of traffic signs. Road markings and reflective road studs will also be replaced.
Highways England project manager Peter Gee said:
This is important work to repair the carriageway and ensure users of the A66 can continue to enjoy safe, smooth and reliable journeys.
As this involves some reconstruction of the carriageway and not just resurfacing, we will have to close one side of the road at times and there will be temporary traffic lights in place around the clock to manage traffic. Were advising drivers to leave extra time for journeys.
The first weeks work involves overnight working only but this will be extended into the daytime from Monday (12 October) with temporary traffic lights in place.
These will be operated manually during the day to ensure drivers are not needlessly held at the lights. A 40 mph speed limit will be in place past the roadworks.
Some side roads off the A66 will be closed overnight for a few nights at a time between 8pm and 6am each night with clearly-signed diversions in place - as the construction work passes them. The scheme is due to be completed by Sunday 20 December.
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.