A two-mile section of the A259 between Warren Hill and Upperton Road will be closed overnight for seven nights from Thursday, December 3.
East Sussex County Council is resurfacing a section of the A259 Church Street, from 100m west of its junction with Victoria Drive to 100m east of the junction with Moat Croft Road.
The closure will take effect from 8pm to 6am, excluding Saturday and Sunday nights, and the road is due to fully reopen on the morning of Saturday, December 12.
Cllr Carl Maynard, East Sussex County Council lead member for transport and environment, said: “As the main coastal route through Eastbourne, the A259 takes a battering from traffic every day and from time to time needs to be resurfaced.
“The work will be carried out overnight to reduce the impact on motorists, and signed diversion routes will be in place.
“We do appreciate that the road runs through a residential area and our contractors will do everything possible to minimise any noise or disruption.”
For drivers approaching from the direction of Seaford, a diversion route will be in place via
Warren Hill, Beachy Head Road, Meads Road, South Street, Gildredge Road and Upperton Road.
For those travelling towards Seaford the diversion route goes via Upperton Road, Eldon Road, Victoria Drive, Upwick Road and Longland Road.
Finally, motorists travelling from Southfields Road should follow Dittons Road, Paradise Drive, Summerdown Road and Pashley Road.
Local residents and businesses have been informed of the work, while more information is available by calling East Sussex Highways on 0345 6080193 or on Twitter @esccroads