Traffic jams from Monday when work starts to improve the junction between the A23 and Preston Drove in Brighton.
The £1.2 million scheme will create new bus and cycle lanes and pedestrian crossings and upgrade the traffic lights.
The road will be reconstructed to improve skid resistance and reduce tyre noise.
Diversions will be in place for about four months and drivers are asked to find alternative routes, wherever possible, to avoid delays.
Brighton and Hove City Council transport councillor Simon Battle said: "These improvements will make it considerably easier and safer for people to travel in the area, especially those who are cycling or walking."
Meanwhile, work continues on the seafront A259 to strengthen arches underneath the road to the east of West Street.
A contraflow has been put into operation so the work can be undertaken safely.
One arch on the north side of the road is being strengthened by drilling steel anchors into the brickwork.
The northern section of another one is being strengthened by infilling with lightweight concrete.
Main contractor Colas is operating extended hours in order to finish the job as early as possible, probably by the end of August.
Coun Battle said: "These are major works to an important and unique road. The reason the work is being undertaken during the busy summer period is it reduces the likelihood of water damage when the tops of the structures are exposed to the elements."
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