The high street in one of the Westcountry's most popular shopping centres is set to close for six weeks after engineers revealed the road is sinking.
It is thought substandard work carried out in Exeter following Second World War bomb damage could be causing the problem, which has continued despite numerous attempts to fix it.
Drainage under the concrete road surface has collapsed and there are fears that if the work is not done the road could collapse altogether.
While the main part of the work is carried out, buses will be diverted away from the lower end of the High Street.
Shops have received letters informing them of the roadworks in the New Year but city centre bosses have pledged to minimise disruption.
Devon's highways bosses and Exeter City Council have agreed that repairs will not start until after the January sales to cut down any impact on traders.
Work will start on January 16 and will be done in phases until March 28, finishing before Easter.
The section of road affected is from Tesco Metro to the area outside Stead and Simpson.
Pedestrian access will be maintained throughout the work. But for a period of six weeks the stretch of road will be shut to buses.
John Harvey, city centre manager, said: "This work to put right a problem with its roots back in the city's post-war construction is critical.
"Great care is being taken over the timetable, with the aim being to minimise the impact on shoppers and visitors to the city centre.
"Our recent track record on managing major utility works in the city centre is an exemplary one and I'll be looking for more of the same."
Andrew McNeilly, manager of the Guildhall Shopping Centre, said: "This work is as necessary as that which was done to the gas mains in Paul Street and North Street in the summer.
"The work has to be done so we just have to take it on the chin."
Peter Shepley, Devon County Council's project engineer for Exeter and East Devon, said: "The road has been settling for some years. We tried to resolve it with specialised foam, but the drainage has collapsed.
"It could be bomb damage – they bulldozed everything after the war and concreted over the top and that has now settled and damaged the pipes."
The first phase of the work will be to put in two new gullies opposite Tesco Metro. This will be done over two nights so buses will not be affected.
The full road closure will begin mid February and no work will be done on Saturdays.
Councillor Stuart Hughes, Devon's cabinet member for highways and transportation, said: "This work is absolutely essential. We will be doing everything we can to minimise disruption but I should apologise in advance for any inconvenience caused."