There will be no peak time intercity trains from Bedford to London for at least two years after May.
From May 20, no East Midlands Trains services arriving into St Pancras between 7-10am will call at Bedford or Luton.
And no East Midlands Trains services leaving St Pancras between 4-7pm will stop at Luton or Bedford.
Services will be suspended while the Midland Main Line Upgrade takes place, with work due to be completed in 2020.
Jake Kelly, managing director for East Midlands Trains, said: “Major investment is being made to improve the railway in Bedford and the surrounding areas, with the £7billion Thameslink programme and the transformation of the Midland Main Line which will deliver the biggest upgrade of this line in almost 150 years, bringing better journeys for customers and representing an investment of over £1billion.
“To enable these major projects to be successfully completed, there will have to be some changes to our services and we appreciate that this will mean inconvenience for some customers.
“Our priority has been to ensure that these customers have alternative transport connections in place with the additional fast GTR services being introduced from May and the replacement coach service from Wellingborough.”
At present a ‘slow’ Thameslink train takes 59 minutes to go from Bedford to St Pancras at 8.04am on weekdays.
But a fast East Midlands Trains service takes as little as 37 minutes.
Off-peak and weekend East Midlands Trains services and Luton Airport Parkway services will not be affected by the changes.