The Euston closure, down to track upgrades at Watford, means journeys will take longer and involve replacement bus services.
West Coast main line passengers are being advised to travel on Thursday, April 14, and Tuesday, April 19, if possible.
It’s bad news for Preston North End fans whose side are in action at Fulham on Easter Monday and those who fancied a long weekend in the capital.
The closure is part of Network Rail’s wider £22millon improvement plan.
Other essential work which will require the railway to be closed at points over the bank holiday includes changes to trains between Liverpool and Manchester due to track maintenance around Liverpool South Parkway, signalling and track improvements around Crewe station and railway foundation stone upgrades on the West Coast main line at Carnforth.
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.
“I’d urge people to travel before and after these big jobs need to close sections of railway, so they have the smoothest journey possible.”