Two-thirds of train operators will be cutting or replacing services this weekend with some entire journeys being replaced by buses.
Rail upgrades have forced 18 out of 25 rail operators to make changes to their services.
Holidaymakers travelling by rail between Luton airport and St Pancras International in London will be diverted onto buses for the entire journey on Sunday.
There will also be long delays on the West Coast main line on Saturday and Sunday, which will affect rugby league fans travelling from the north-west to London to watch the Carnegie Challenge Cup Final at Wembley.
Passengers on Britain's busiest line will be transferred to replacement buses around Crewe on both days and the journey time between London Euston and Glasgow will almost double to 7 hours 54 minutes.
East Anglia will also be badly hit with parts of the line between London Liverpool Street and Ipswich and Norwich closed throughout the entire three days. The normally direct journey will double from 1 hour 48 minutes to 3 hours 23 minutes on two trains, two replacement buses and the London Underground.
The East Coast mainline between London King's Cross and Scotland will also have delays and reduced services. And travellers to the South West are warned to reserve seats to avoid standing for hours.
Network Rail insisted that passengers would face less disruption than last year with 1,700 more trains and 95% of the normal weekend service running.
A spokesman told the Metro: 'We advise passengers to check with their train operator or National Rail Enquiries before they travel - but there will not be huge amounts of disruption."
Motorists are also likely to suffer delays after the Highways Agency said it could not suspend all roadwork schemes for 'safety reasons'.
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