Industrial action by train drivers who are members of the Aslef union will prevent passengers using the busiest station outside of London.
Avanti West Coast, CrossCountry, London Northwestern Railway and West Midlands Railway have urged people not to travel.
Transport for Wales is not involved in the strike but its hourly service which runs through Birmingham New Street will terminate at Wolverhampton.
TfW is advising customers to only travel between Wolverhampton and Shrewsbury if their journey is essential as services are likely to be extremely busy.
Martin Colmey, operations director for Network Rail’s Central route, said: "It’s frustrating and disappointing that Birmingham New Street will be closed this Saturday because of the train drivers’ strike.
"We will have staff on hand to help people passing through the station but please be patient on what will be a very difficult day for everyone. Our advice is to contact your train operator for the latest information on ticketing, services and refunds. The National Rail Enquiries website at www.nationalrail.co.uk is the best place to plan your journey for a different day."
People will still be able to access the station concourse which provides a key pedestrian route across the city centre, but all ticket gates will be closed with no access to platforms. Network Rail staff will also be on hand to help.