Passengers are being urged to travel either side of the Easter bank holiday due to work on the railway.
Network Rail says between Good Friday and Easter Monday, London Euston station will be closed to mainline train services due to major track upgrades in Watford and HS2.
The rail body is advising the best time to travel will be on April 14 and 19.
It means there will be no London Northwestern trains running from stations including Watford Junction, Bushey, and Kings Langley in the direction of London or Milton Keynes.
Instead trains will start and finish at Milton Keynes, Network Rail says. Rail replacement buses are set to be available, particularly for those travelling north.
London Overground services will still be operating from Watford Junction towards London, but not to Euston, and the Metropolitan Line will also be available from Watford station by Cassiobury Park, although there is a reduced timetable.
Network Rail says it is investing £22 million this Easter in order to improve future journeys for passengers and freight on the West Coast mainline which runs from London to the north west of England.
The work has caused controversy with Liverpool and Manchester City fans needing to find alternative ways of reaching Wembley Stadium for the FA Cup semi final that weekend.
Dave Penney, Network Rail passenger director for the North West and Central region, said: "There is never an ideal time to shut the railway and we have to carefully balance the best time to do this essential work with the needs of our passengers.
"Long bank holiday weekends continue to give our engineers the time they need to close the railway for complex jobs like track replacements and bridge overhauls while disrupting the fewest number of people.
"Our advice this Easter is to travel either side of the bank holiday on Thursday 14 and Tuesday 19 April, and to plan ahead by checking National Rail Enquiries to see how your journey could be impacted by our essential £22m upgrades to improve the railway for the future."
Passengers should plan ahead at www.networkrail.co.uk/wcml, check with their train operators or visit www.nationalrail.co.uk for the latest journey information, or by following #EasterRailWorks on Twitter.
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