The A259 between Hastings and Rye will be closed for resurfacing work throughout February.
Highways England said the works will be carried out on the 12-mile stretch of road between the A268 (Skinners roundabout, Rye) and the A2101 (Queens Road, Hastings).
The works will be carried out overnight, meaning the road will be closed from 8pm to 6am most nights throughout February.
Highways England said the A259 will be closed from the A268 (Rye Road) and the junction with the A2101 Queens Road from 8pm on Friday (January 31) to 6am on February 1 (Saturday).
Highways England has warned motorists to expect disruption everyday between February 3 and February 8, February 10 and February 15, and from February 17 to February 22.
The disruption will affect traffic heading in both directions, Highways England added.
From Monday, February to Friday, February 28, there will be a full closure of the A259 between Skinners Roundabout in Rye to the junction with the B2093 (The Ridge) in Hastings.
In a letter to residents, Highways England said the purpose of the overnight closures was to undertake resurfacing of the roads.
They said the work is taking place on the A259 between Strand Bridge at the junction with Sea Road, Winchelsea and Harbour Road, Rye, and also between Guestling Thorn at the Butcher’s Lane junction and Broad Street, in Icklesham.
Diversions will involve taking longer routes around the area while escorted limited access will be provided for residents.