This 200-metre-long bridge carries the M60 over the River Mersey and Palatine Road near Didsbury.
The complexity of the project will see the M60 lifted by five millimetres so the work can take place.
Bridge specialist Mabey Hire has been brought in to create temporary structures to support the motorway while main contractor Balfour Beatty carries out repairs to the 15 concrete columns that the M60 bridge currently rests on.
Two of the columns were repaired last year and work has now started on the next phase of the project involving two columns at the east end of the bridge.
Around 800 tonnes of motorway will be lifted above each column using 44 remotely-operated hydraulic jacks, which can be controlled with a tenth of a millimetre precision.
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These measures will ensure around 80,000 drivers continue to use this stretch of the motorway with no sign of the ongoing works.
Mark Mosley, project manager at Highways England, said: "The bridge over the Mersey has been there since the motorway first opened in 1974 as part of what was then the M63, and it's beginning to show its age.
"We'll be using teams of specialists to lift up the motorway by a few millimetres and then carry out concrete repairs to the bridge columns, and will be able to keep the road open to drivers throughout the project.
"The repairs will help keep the bridge safe for decades to come, so tens of thousands of drivers can continue to use it every day on a key route across the Mersey."
The bridge was originally constructed using reinforced concrete in the early part of the 1970s and some of the steel inside the concrete has now begun to rust. Once the hydraulic jacks are in place, contractors will begin work on repairing the bridge columns.
The motorway was lifted away from a column under the anticlockwise carriageway last week and will be raised above another column overnight on Thursday 12 March.
The anticlockwise carriageway will be closed from 10pm until 6am between junction 5 (Didsbury) and junction 3 (Cheadle) with a diversion taking drivers along the A5103 Princess Parkway, A560 and M56.
Work on the Palatine Road bridge will be carried out in phases and all the repairs are due to be completed by 2023.
