Rail passengers face “significant disruption” as CrossCountry runs a reduced timetable over the bank holiday, with no services on Saturday.
National Union of Rail, Maritime and Transport Workers (RMT) members will walk out on Saturday and Monday, but Sunday trains could also be cancelled, the rail firm said.
Passengers have been advised not to travel on Saturday and warned there will be a “very limited service” on Monday.
The RMT said it was “seeking further talks with management to bring about a negotiated settlement”.
On Monday there will be no CrossCountry trains between Birmingham, Reading and the south coast, or Leicester, Cambridge and Stansted Airport, and only a limited service to the South West and north of York
Planned engineering work in the West Midlands will also impact the services that do run, meaning some journeys will take longer, the train operator said.
Shiona Rolfe, CrossCountry’s managing director, said: “We are disappointed for our passengers that the RMT has announced strikes.
“It is hugely disappointing to not operate any services on Saturday, knowing the inevitable disruption to many of our passengers’ journeys over the bank holiday weekend.
“We are committed to reaching an agreement with the RMT and remain available to continue talks.”
An RMT spokesperson said: “Our members have voted strongly in favour of industrial action, and we are seeking further talks with management to bring about a negotiated settlement.”
Union sources said the strike centred on claims CrossCountry had failed to honour agreements on staffing, safety, and pay.
The company has urged passengers to check before they travel and if possible travel on either side of the bank holiday weekend, or claim a full refund.