Highways England has issued a notice outlining its plans for the work – along the A49 from Dobbies Roundabout in Shrewsbury to Leominster.
Workers will be painting fresh road markings and replacing signs during the 12 weeks.
Highways England said the work would be carried out overnight – between 8pm and 6am – and will only be taking place on weekdays.
The work starts on Monday, October 11 and will also include lay-by closures along the route which is the major artery from Shrewsbury to South Shropshire and Herefordshire.
Throughout the three months there will be a series of signposted diversion routes, taking in the A4110, the A4113, the A4117, the A44, the A456, the A458, the B4364, the B4365, the B4368 and alternative junctions of the A49 and the A5.
A number of other roadworks are also planned in the Shropshire Council area over the coming weeks.
Sutton Road in Shrewsbury will be closed to cars to allow for Severn Trent to carry out work.
The water company says the work will be “maintaining flow monitoring equipment in the dirty water system to help prevent drains backing up into properties and streets”.
The closure will start at 10pm on October 7, with the road reopening at 6am on October 8.
Shropshire Street in Market Drayton will be closed for a day to allow workers to repair “a defect” in the road.
The closure will run from 9.30am to 4pm on October 10.
Meanwhile Beatrice Street in Oswestry will be closed to cars from 8am to 7pm on October 10.
Drury Lane, near Minsterley will be shut for two days for Severn Trent Water to carry out a boundary box installation.
The closure will start on Tuesday, October 5.
Telford & Wrekin Council is also proposing a series of new speed limits for roads in the borough.
The council has included sections of a number of roads under plans for 20mph limits.
These include Burcot Road, Davids Bank, Drummery Lane, South View, Station Road, The Avenue, Tiddlecross Lane, Turreff Bungalows, Wrekin View and Blacksmiths Lane.