Rail users travelling between Scotland and England will face three months of disruption as modernisation work gets underway on Saturday.
The West Coast Main Line, which connects both Glasgow and Edinburgh to Carlisle, will close for 16 days during the first phase of an upgrade to Carstairs Junction.
Network Rail has confirmed that the work will see significant disruption to services until June, including diversion and longer journey times.
The closure of the major line between March 4 and March 19 will mean no direct services linking either Edinburgh or Glasgow to Carlisle.
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It comes as part of a £164m Scottish Government investment to modernise Carstairs Junction for passenger and freight services.
Engineers will simplify and upgrade the track-layout to clear an existing bottleneck on the network - helping it cope with high passenger and freight demand.
Work on this strategically important route will be complex and Network Rail split it into three phases to limit the chaos cause to travellers.
Network Rail Scotland route director Liam Sumpter said the junction was at "the end of its life cycle".
He added: “By completing this crucial upgrade work we will improve the capabilities and reliability of this strategically important junction, providing better future journeys for passengers and more capacity for freight.
“There’s never a good time to close such an important line but this is a huge and extremely complex piece of work that will safeguard the future of the route for years to come.
“We appreciate that this will cause some inconvenience and would like to thank customers for their patience during this time.”
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The closure of the junction will affect cross-border operators including Avanti West Coast, Caledonian Sleeper, CrossCountry Trains, London North Eastern Railway and TransPennine Express.
Replacement buses and diversionary routes will be in place.
Phase two of the work, which will take place between March 20 and April 27, will allow part of the junction to re-open on weekdays.
Some trains will therefore be able to run directly to Edinburgh and via diversion routes to Glasgow.
The final phase, between April 22 and June 4, will see most services return to normal during weekdays but the junction will be fully closed each weekend.
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