The essential upgrade works will take place at Rannoch viaduct, just north of Rannoch station, as part of a £1.6m investment to extend the operational lifespan of the structure.
New timbers will be installed and the metal girders will be repaired, cleaned and repainted on the viaduct, which carries the line across the world-famous Rannoch Moor.
Engineers will work around the clock from March 16 to complete the project before the line reopens for service on Monday 25 March.
While the work is ongoing, services between Glasgow Queen Street and Fort William/Mallaig will be impacted with buses replacing trains between Crianlarich and Fort William and between Fort William and Mallaig.
Buses will also replace trains from Tulloch, Roy Bridge & Spean Bridge stations to Fort William but there will be no services to Rannoch and Corrour during the closure.
Services between Glasgow Queen Street and Oban will operate as normal throughout the closure.
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Zoe Monkhouse, Network Rail's project manager for the Rannoch viaduct project, said: "The work we are undertaking in March is essential and cannot be delivered without closing the railway.
"We know that closing the railway at any time is never ideal, however we always endeavour to plan our work for when fewer people are travelling on the railway and at a time which reduces overall inconvenience for the travelling public.
"We understand that this is not great news for those making plans to travel to visit family or friends or for leisure purposes, but our team will be working around the clock to deliver these works safely and on time.
"We thank passengers for their patience and understanding and apologise for any inconvenience this may cause."
Phil Campbell, ScotRail Customer Operations Director, said: "We know the impact this line closure will have on customers, and we will be doing everything we can to keep people moving during the work.
"Replacement buses will be in operation, but journey times will take longer, and we encourage customers to check before they travel using the ScotRail website, app, or social media channels."
In addition to the work on the viaduct, Network Rail will also improve multiple sections of track between Tyndrum and Roy Bridge and between Spean Bridge and Arisaig.
Signalling upgrades will take place between Fort William and Spean Bridge and drainage enhancements will go ahead south of Rannoch station.
The works at Rannoch viaduct will involve replacing 50 longitudinal timbers (way beams), which run the length of the 208m structure and support the rail going over the steel bridge. The softwood timbers are life-expired and will be replaced with hardwood alternatives, with the existing baseplates and rail also being renewed.
These are part of ongoing efforts to enhance the safety and reliability of the railway for years to come.
If you have any questions about this work, you can contact Network Rail's 24-hour national helpline on 03457 11 41 41. For the latest information and progress updates follow on Twitter @NetworkRailScot.
