Stamford Street will be closed to eastbound traffic for three weeks starting this weekend.
Southern Gas Networks will be carrying out works at the eastern end of the street.
The eastbound road closure begins on Sunday 8 February and continues until Monday 2 March.
The lengthy diversion will put extra pressure on bus services which are already being used by more passengers than normal due to the part-closure of London Bridge Station.
For the latest local news and events direct to your inbox every Monday, you need our weekly email newsletter SE1 Direct.
7,000+ locals read it every week. Can you afford to miss out?
Read the latest issue before signing up