Avanti West Coast has slashed its timetables and suspended ticket sales for a month.
The company said severe staff shortages, as well as "unofficial strike action" by ASLEF members, has caused services to be reduced dramatically "until further notice".
As few as four trains per hour - from London Euston, one to each of Glasgow, Liverpool, Manchester and Birmingham - will run from Sunday, 15 August, in an attempt to stop short-notice cancellations that have plagued the service in recent months.
Every two hours, services will run through to Edinburgh, via the West Midlands, while there will be a shuttle service between Crewe and Holyhead, plus a limited through service between Euston and Chester of one a day.
Journeys between Manchester and London Euston are the worst affected by the cut, with train frequencies reduced from three per hour to just one.
A spokesperson said: "This decision was not taken lightly, and we are sorry for the enormous frustration and inconvenience this will cause."
Avanti has urged rail unions to "engage in meaningful industry reform talks around modernising working practices and developing a railway fit for the 21st century."
Adding that they "remain open for talks at any time."
The company has suspended ticket sales for travel from 13 August until 11 September while the new schedule is finalised in order to minimise disruption.
It expects tickets for the first week of that period to be back on sale soon and tickets for the following weeks will be released on a rolling, weekly basis.
ASLEF has insisted its members at Avanti are not involved in strike action before a walkout on 13 August, in a long-running dispute over pay and conditions.
Drivers at CrossCountry, Greater Anglia, Great Western, Hull Trains, LNER, London Overground, Southeastern and West Midlands Trains will also strike that day.
What if I have bought a ticket for a cancelled service?
Passengers who have already bought tickets for trains that are removed from the timetable will be able to travel on the service before or after their booked train.
If they no longer want to travel they can claim a full, fee-free refund from the point of purchase.
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