Rail timetables are changed every May and December, but rarely to this degree.
Network Rail is promising quicker journeys and thousands of extra seats every day, following a £4bn investment over the past decade.
The changes promise a cut of 15 minutes to journey times between London King’s Cross and Edinburgh and 10 minutes between Edinburgh and York.
Network Rail says the rail line, which is used by several operators, will have improved connectivity between Scotland, North East, England, Yorkshire and London.
One of the companies using the line, LNER, called the changes “transformational” and said it expected to run 10,000 additional services per year.
Ellie Burrows, Eastern regional managing director for Network Rail, said: “The industry has been preparing for many years for the new timetable.
“Our priority now is to continue working together to deliver the long-term benefits of this timetable change, the biggest in over a decade, for our passengers and the communities we serve.”
The changes will also see Northern launch a new hourly fast service between Leeds and Sheffield.
Another operator, Avanti, says there will be more trains between London and Liverpool.
Meanwhile Transport for Wales is introducing more services for Chester, Wrexham and Swansea.
The changes are the biggest since May 2018 when a timetable update triggered major disruption and cancellations on some services.
That led to a full review and eventually the Labour government’s decision to create Great British Railways and bring the industry under state control.
Travel expert Simon Calder said he was “pretty confident we won’t see the complete collapse of a network, as we did when the Thameslink line had its timetable completely reconfigured in 2018 – that was an absolute shambles”.
“There has been an awful lot of thought and time that has gone into this and the whole idea is to extract the maximum possible capacity from Britain’s Victorian rail network without jeopardising reliability.”