Only 20% of services will run and some places will have no trains on Wednesday, Network Rail says.
People are being told only to travel by train if necessary during the latest national strikes by rail workers.
Some 40,000 members of the RMT union working at Network Rail and 14 train operators will walk out on Wednesday.
It comes after talks over pay, jobs and terms and conditions failed following the biggest rail strikes in 30 years over three days in June.
Network Rail said only 20% of services will run and some places will have no trains at all on Wednesday.
For example, there will be no trains into or out of Blackpool, Portsmouth and Bournemouth.
In a bid to minimise disruption, Network Rail has published a special timetable for Wednesday, with trains set to start later and finish earlier than usual, between 07:00 and 18:30 BST.
On Wednesday, the last trains from London will leave for Edinburgh at 14:00, for Birmingham at 16:03 and Manchester at 15:40.
RMT general secretary Mick Lynch said the union would continue to try to reach a deal with Network Rail ahead of Wednesday.
“If we could get a breakthrough then we wouldn’t have to take strike action but there’s a big gap between the parties at the moment,” he told BBC Radio 4’s Today programme.
“So I’m not going to raise false hopes but we are constantly in dialogue with all of the elements of the industry.”
All train operators, including Transport for London, will be affected by the strike as Network Rail’s signallers control train movements across Great Britain.
The knock-on effects of the disruption are expected to roll in to Thursday, Network Rail said. Further RMT strikes are also planned for 18 and 20 August.
Wednesday’s strike will disrupt travel to the Women’s Euro 2022 semi-final in Milton Keynes and comes a day before the Commonwealth Games begin in Birmingham.
On Saturday, there is a separate walkout by train drivers’ union Aslef at Arriva Rail London, Greater Anglia, Great Western, Hull Trains, LNER, Southeastern and West Midlands Trains.
This is also the first day of the English Football League season.
Andrew Haines, Network Rail chief executive, said: “Despite our best efforts to find a breakthrough, I’m afraid there will be more disruption for passengers this week as the RMT seems hell-bent on continuing their political campaigning, rather than compromising and agreeing a deal for their members.”
Passengers with an advance, off-peak or anytime ticket for 27 or 30 July can travel the day before or up to and including 2 August, Network Rail said.
They can also change their tickets to another date, or get a refund if their train is cancelled or rescheduled.
Those with season tickets for a month or longer who choose not to travel on 27 or 30 July can claim compensation through the delay repay scheme.