Passengers face major disruption over Christmas as Network Rail carries out 300 engineering projects.
It comes after train cancellations hit a record 3.8% in the year to October 15, according to data from the Office of Rail and Road.
And the RMT has warned more strikes are “highly likely”.
Greater Anglia, c2c and Stansted Express services will be hit by the closure of London Liverpool Street for maintenance.
There will be no Southern or Gatwick Express services to or from London Victoria over that period.
And Avanti West Coast trains between London Euston and Glasgow Central will be on a reduced timetable between Christmas Eve and December 30.
Network Rail said over 95% of the network will be open but urged travellers to plan carefully.
Industry body the Rail Delivery Group blamed a reduction of staff due to the pandemic for the record rate of cancelled services.
Norman Baker of pressure group Campaign for Better Transport said: “Cancellations on this scale are unacceptable.”
A spokesman for industry body the Rail Delivery Group said: "We understand that reliability and punctuality of train services are top priorities for rail customers.
"As with many other areas of the economy, the Covid pandemic has had a long-term impact on our services.
"The pandemic reduced the number of drivers and other staff who could be trained during 2020 and 2021, while staff absence rates have inevitably been higher since the pandemic began.
"Regrettably, these absences often lead to last-minute cancellations.
"The number of significant extreme weather events - such as heatwaves and storms - is also increasing and these can have a severe impact on services."