Overnight closures of sections of the A27 between Patcham and Falmer, and Lewes and Polegate, begin on Monday, January 15.
A full eastbound closure of the A27 between the Patcham interchange and A270 junction at Falmer takes place for four nights for resurfacing.
The stretch will be closed between 8pm and 6am, and again on Sunday, January 21.
Diversions will be in place and Highways England said the works should be completed by the end of January.
Also from Monday, a full closure of the trunk road between Lewes and Polegate – from Burgh Lane to The Street turnings – will take place for two nights, from 8pm to 6am, for resurfacing.
On Wednesday, January 17, there will be a full carriageway closure between Pound Lane and Milton Street for four nights between 8pm and 6am.
A clearly signed diversion will be in place via the A22 and A26.
Elsewhere, work to build a new traffic light controlled junction on the A259 between Sandhurst Lane and Broadoak Lane continues this week.
Work is expected to be completed by February.