Shropshire Council said "significant improvements" will be carried out between July and November on the A458 Bridgnorth bypass.
The roundabout approaches between the A458/B4373 Wenlock Road junction and the Stourbridge Road roundabout will also be included in the works.
Steve Brown, Shropshire Council’s highways, transport and environmental maintenance manager, said it was the first significant work carried out on the road since its creation.
He said: “The Bridgnorth bypass scheme will see some important work carried out on one of the county’s most important roads, and road users will see big improvements once the work is complete.
"I hope most people will agree that this work is important, and that the long-term benefits will far outweigh the short-term inconvenience.
"I thank them in advance for their patience and understanding while this work is carried out.”
The bypass project will see the replacement of bridge expansion joints on the Bridgnorth River Severn Bridge, along with concrete repairs to the bridge and works on the bridge parapets.
The Severn Valley Railway overbridge will also be repainted and the A458 and the roundabout approaches will be resurfaced.
Road signs and road markings will be replaced and refreshed, and footpaths will be repaired.
The street lighting and safety barriers will also be updated, and drainage improvements will be carried out.
Work is due to start on July 4 and is expected to be finished by November 10.
Shropshire Council said a number of "key dates" had been identified for those using the road including from July 4 to August 2, when traffic signals will be put in place on and around the Ludlow Road Roundabout for resurfacing work.
From July 4 to August 7, a combination of traffic signals and lane closures will be in place on the three-lane section between the Ludlow Road Roundabout and the Oldbury Road Overbridge for resurfacing work.
Night time road closures will be held between August and October, with a series of five 24-hour closures during the first two weeks of October.
Access to local businesses and properties will be maintained while work is carried out.
For more information, visit Shropshire Council's roadworks website at shropshire.gov.uk/roadworks.