Work to replace sections of track and overhead electric cables and maintain bridges, tunnels and trackside equipment is being done on the route between London Euston and Cumbria.
Martin Frobisher, managing director of Network Rail’s London North Western route, said: "We recognise there is never an ideal time to shut the railway for our must-do work.
"Bank holidays are the least disruptive time to do it, when fewer passengers use the railway compared to the working week.
"That way we can do the maximum amount of work while impacting the fewest people.
"Sometimes a closure is the only way we can carry out major work like replacing track or improvements to overhead electric lines.
"Train companies and Network Rail have worked together to minimise disruption for customers by doing a lot of work over the recent bank holidays. The alternative would have been closing the line over multiple weekends throughout the summer.”
Ahead of the Bank Holiday weekend on May 25 to 27, passengers are being advised to plan their journeys at www.nationalrail.co.uk, when sections of the West Coast main line will be closed between London Euston and Milton Keynes, and Warrington and Cumbria.
Where the line is open trains will be running but customers will have longer journeys, fewer available seats, and may need to use rail replacement buses.
Robert Nisbet, regional director for the Rail Delivery Group, which represents the railway, said: "This vital engineering work is part of the rail industry’s plan to add more services, improve punctuality and make journeys better, and as fewer people travel on bank holidays than on a normal weekday, we’re keeping disruption to a minimum.
"We encourage people who are planning to take the train over the May bank holidays to check before they travel by visiting nationalrail.co.uk or speaking to their train operator."