The main road into Torbay and south Devon will be closed for three nights while construction starts on a bridge over the A380.
Friday night will see the start of the £4m Haldon Chalets safety scheme to improve two dangerous junctions.
The road will be closed from 2000 until 0600 while new 40m (130ft) bridge beams are lifted into place.
Torbay Council said it hoped the scheme would reduce collision rates at the top of Telegraph Hill and at Mamhead Cross.
Important scheme
A council spokesperson said: "The new junction layout is something which local people have long been calling for and we are sorry for any inconvenience caused by the temporary closures.
"We can now look forward to completion of this important scheme."
Both outer lanes of the A380 and both central reserve crossovers at Haldon Chalets will be closed for the length of the work.