The Settle to Carlisle route will be used by rail firm Avanti in the new year while a bridge over the M6 is replaced.
The 60-year-old Clifton bridge, which crosses the M6 near Penrith, has reached the end of its life. Work to demolish and replace the structure will take place in January.
It means the West Coast Main Line will be blocked between Carlisle and Preston from January 1 to January 14 – and the M6 from Junction 39 to Junction 40 closed – while work is carried out.
But Avanti West Coast has announced it will use its trains on the historic Settle to Carlisle line.
It said it had worked closely with Network Rail and the wider railway industry and will run its new bi-mode Class 805 Evero trains along the route.
It will run a shuttle service around every two hours between Preston and Carlisle non-stop via the Settle to Carlisle route.
The historic 73-mile-long railway line, is being used as a West Coast Main Line diversionary route for the first time in over 10 years.
Last month, Avanti West Coast ran a trial using a 10-carriage Evero train on the route as part of their planning and preparations ahead of the January work.
Its Class 805 trains, which were introduced in June last year on the North Wales and West Midlands routes, are bi-mode, meaning they can run on electric or diesel power.
People travelling from Liverpool, Birmingham, Manchester and London to Scotland will be advised to go via the East Coast Main Line using other operators.
For those wishing to travel to and from Lancaster, Oxenholme and Penrith, a rail replacement bus service will be in operation.
The full train timetable will be published in early next month.
During the two weeks, there will be some minor changes on the routes currently served by the Class 805 Evero trains as they will be used on the Settle to Carlisle diversion.
People travelling during this period are advised to check before they travel.
