The major concrete repair and waterproofing scheme affects the Oldbury viaduct, between junctions 1 and 2 of the motorway.
Highways England is undertaking the work as part of a major government investment to build a modern and resilient road network.
Built in the early 1970s, the structure itself is safe but work needs to be carried out to protect it for the future.
To begin with traffic travelling between the affected junctions will experience narrow lanes and a 40mph speed limit when work gets under way after Easter.
And for the first time upgraded travel information signs linked direct to the Highways England regional control centres that monitor traffic flows will provide real time travel advice to motorists about the quickest journey times.
In the early summer speeds will drop to 30mph for safety reasons as a contraflow is introduced. Slip roads will be kept open throughout.
Highways England delivery manager, Colin Jackson, said:
We will be starting work on a major concrete repair and waterproofing scheme at the Oldbury viaduct, between junctions 1 and 2 of the M5 in the West Midlands, this month.
At a cost in excess of £100 million Highways England is delivering a huge investment that will support economic growth locally and in the wider West Midlands.
Motorists travelling from across the country will be encouraged to consider alternative routes such as the M42 and M6 to keep congestion to a minimum on the M5 and surrounding roads while work takes place.
Highways England is keeping the haulage, freight and distribution industries informed of the essential work, expected to last until Spring 2019, to allow their lorry drivers to plan ahead and seek alternative routes.
People are also being asked to consider car sharing or use alternative methods of transport where possible.
Highways England will continue working with businesses and hauliers as well as local authority partners and other organisations as the scheme gets under way.
For more information visit the scheme website.
Members of the public should contact the Highways England customer contact centre on 0300 123 5000.
Journalists should contact the Highways England press office on 0844 693 1448 and use the menu to speak to the most appropriate press officer.