The stretch of Sunningdale Road from Adelaide Street North to Richmond Street will be closed starting Tuesday.
The City of London says the closure is expected to last for about two months.
Area infrastructure work is being done, with the focus on channel work and culvert upgrades to improve drainage and stormwater management.
Westbound drivers and cyclists will be redirected along Adelaide to Medway Road, while eastbound traffic will be redirected along Richmond to Medway.
Local traffic will be able to access Canvas Way from Sunningdale.
Cyclists and pedestrians will not be able to access the area.