The second part of Phase 2 of the widening of Golf Links Road is scheduled to begin on Thursday and will close the busy thoroughfare to through traffic.
City officials say the work, between John Street Road and Linden Court, could take up to five months.
A posted detour routes will include Oliver Road, Balmoral Street and John Street.
Local access to residential streets, including River Terrace, as well as businesses along the stretch and Thunder Bay Regional Health Sciences Centre, will be made available during construction.
The initial work, which begins on Thursday, will include a stretch between Riviera Drive South and Riviera Drive North, but will include a full road closure expected to last up to four weeks.
Motorists are being advised to seek alternate routes during construction and to drive cautiously when traveling through the area.