From this weekend, Tooley Street will be part-closed to eastbound motor traffic until February 2018 for work on the redevelopment of London Bridge Station.
In addition, that section will be completely closed for all three days of the May Day bank holiday weekend.
Most bus services will be diverted via Bricklayers Arms, though eastbound RV1 buses will cross London Bridge instead of Tower Bridge.
"One of the biggest challenges of rebuilding London Bridge has been minimising disruption, not only to passengers but also to our neighbours," said Andrew Hutton of the Thameslink Programme.
"The part-closure of Tooley Street is unavoidable as we enter the last stages of the project and my team and I have been planning this for many years to make it as safe and as seamless as possible.
"We are doing everything we can to minimise that, including allowing for cyclists to continue to ride both ways down the street on a separate path.
"The new piazza and massive new entrance we are building will be a huge improvement over what we have right now, and while a degree of disruption is inevitable, it will be worth it in the long run."
Leon Daniels, managing director of surface transport at TfL, said: "We've been working closely with Network Rail to minimise the impact of the vital London Bridge railway station rebuild and to ensure Londoners and key stakeholders have the travel advice they need.
"All eastbound traffic between Duke Street Hill and Tooley Street will be diverted – except for bicycles – and some bus stops will be temporarily relocated. Our advice to customers is to check before they travel and allow more time for their journeys.
"While the closure is in place our 24-hour traffic control centre will manage traffic in the area, including the use of our intelligent traffic signals to minimise delays."
• More information at www.thameslinkprogramme.co.uk/tooleystreet