Network Rail said it will carry out work on more than 300 projects across Britain between Good Friday and Monday, causing a number of lines to be closed.
The most significant impact will be at London Euston - the UK's 10th busiest railway station - which will have no services to or from Milton Keynes on Saturday and Easter Sunday, and a reduced timetable on Good Friday and Monday.
That is because of work including renewals of overhead electric lines and drainage improvements.
Services on the West Coast Main Line between Saturday and Monday will start and terminate at Carlisle, with replacement buses serving stations to the north.
Platforms 1-8 will be closed at London Victoria, meaning no Southeastern trains will serve the station over the four-day bank holiday period.
Services will be diverted to London Bridge or London Cannon Street.
Engineering work in the Southampton and Brockenhurst areas will close various lines in the region.
Helen Hamlin, Network Rail's director of system operations, said: "The vast majority of the rail network will be open as usual for people wanting to travel over the Easter bank holiday, but there will be changes to services in some areas, so we're asking passengers to plan ahead and check before they travel.
"We carry out a large amount of our work over the Easter period as passenger numbers are lower than they typically would be, disrupting fewer journeys, and the two bank holidays either side of the weekend give us a unique opportunity to get more work done whilst keeping disruption to a minimum."
Network Rail said it will deliver investments totalling £86 million over the Easter period.
Meanwhile drivers are being advised to prepare for congestion around town and city centres, retail parks and major routes such as the M6 at Birmingham and around the Blackpool area, the south and western section of the M25 between the M23 and M40, the M5 at Bristol and the A303 in Wiltshire.
The AA estimated that 19.1 million people in the UK will drive on Good Friday, with 18.5 million hitting the road on Saturday and 18.2 million on each of Easter Sunday and Monday.
Steven Skeates, deputy chief meteorologist at the Met Office, said there will be "changeable weather for many" during the bank holiday weekend.
An area of low pressure could bring "heavy and possibly even disruptive rain" on Good Friday for parts of south-west England, Northern Ireland and South Wales, he added.
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RAC breakdown spokesperson Alice Simpson said if the heavy rain becomes a reality "many drivers may have their journeys disrupted as they set off for day trips and long weekends".
She added: "It's vital to plan ahead and be prepared for trips to take longer because of the wet weather and the expected getaway congestion."
Ms Simpson said an estimated 6.2 million people are "undecided" on when they will travel for an Easter leisure trip, which means "any sign of sun" could spark "big jams".
National Highways said it has removed roadworks from 1,127 miles of motorways and major A roads in England, meaning 97.5% of its network is free of traffic cones for Easter getaways.
Tourism authority VisitEngland estimates that around 10.6 million British adults are planning to take a holiday in the UK over the bank holiday period.
Meanwhile travel trade organisation Abta said approximately 2.2 million Britons will head overseas during the long weekend, with Good Friday being the busiest day for travel.
Some 11,282 flights are scheduled to depart UK airports between Good Friday and Monday, according to aviation analytics company Cirium.
That is 6% more than during last year's Easter, but remains 4% down from Easter 2019.
The most common international destinations for UK departures this Easter are Dublin, Amsterdam, Malaga, Alicante and Mallorca.