Train services will be severely limited, only run between 7.30am and 6.30pm, and some routes will be closed altogether amid national industrial action.
Thousands of specially-trained and fully qualified back-up staff will step in during the walkout - which has been called by the RMT union - to keep vital services running for those who need them.
But with only around 10 per cent of services running and some lines closed completely, passengers are asked to only travel by train if they must.
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Trains are set to start later and finish much earlier than usual, between 7.30am and 6.30pm, leading Leeds station to close at 7pm.
Only 14 trains are planned to run in and out of the station each hour on Wednesday, compared to the usual 40-50.
Those who really need to travel should allow extra time and check their last train times.
Matt Rice, North and East route director for Network Rail, said: “Unfortunately, ongoing industrial action will once again cripple train services for passengers in Yorkshire and the North East on Wednesday.
“I can only apologise for the impact this will have on people’s plans and on their daily commute.
"I’d urge those who absolutely need to travel by train to plan ahead, check their journey and expect significant disruption.”
Passengers should also expect disruption on the morning of Thursday, July 28 with a later start to services as railway workers return to their duties.
Separately, ASLEF has called strike action across eight train operators on Saturday, July 30 that will significantly disrupt some routes, so passengers are asked to check their journeys before travelling over the weekend as well.
Further information for passengers is available on the National Rail website.