Tower Bridge, which is used by some 21,000 vehicles every day, will be shut off to drivers from October.
The City of London Corporation said the closure will allow maintenance work to be undertaken on the 122-year-old monument.
A spokesman for Transport for London added that the impact of the work will be minimal.
One of the main goals of the project will be to redo the waterproofing of the archways in the approach to the bridge, which were last worked on when they were originally built at the end of the 19th century.
Construction staff will also replace timber decking on the bridge, stretches of which were laid in the 1970s, and resurface the roads and walkways.
The closure comes after it was announced that nearby Tooley Street will be shut until 2018, so that Network Rail can rebuild London Bridge railway station.
Tower Bridge, which took eight years to build before its official opening in 1894, will remain accessible to pedestrians on all but three weekends, with the viewing galleries along its walkways also staying open.
Leon Daniels, TfL’s managing director of surface transport, said: "We've been working closely with the City of London to minimise the impact of the vital refurbishment of Tower Bridge and to ensure that Londoners have the travel advice they need.”
He went on to advise motorists to check their route prior to travelling and to allow extra time to get to their destination.
Drivers can use the RAC’s Route Planner to plan their journeys, as well as to get information on traffic updates and work out travel mileage.
Chris Hayward, chairman of the planning and transport committee of City of London Corporation, said: "This decision to close Tower Bridge to vehicles has not been taken lightly, and this course of action has been taken after extensive consultation and planning in conjunction with numerous stakeholders.”
"We will use this time to repair, refurbish and upgrade London's most iconic bridge, which has gone without significant engineering works for more than 35 years.”