The RMT's decision to proceed with train strikes next week will "punish millions of people", the transport secretary has said.
Grant Shapps warned the UK is "now on the cusp of major disruption which will cause misery for people right across the country".
He also claimed the union has been repeatedly urged not to proceed with the "damaging" industrial action - and focus on negotiations instead.
Mr Shapps said teenagers preparing for their exams will face the additional stress of changing their travel plans, while patients may have to cancel hospital appointments.
He added: "Many people who do not get paid if they can't get to work face losing money at a time they simply can't afford to."
Talks have failed to resolve a bitter row over pay, jobs and conditions - and next week's rail strikes are set to be the biggest in decades.
Unions accused of 'bribing workers'
The walkouts will take place on Tuesday 21, Thursday 23 and Saturday 25 June.
Network Rail has warned the strikes will cause six days of disruption because services will be affected on the days in between.
RMT general secretary Mick Lynch said thousands of jobs were being cut across the rail networks, and workers were facing below-inflation pay rises.
Some of the larger trade unions behind the action have now also been accused by Business Secretary Kwasi Kwarteng of "bribing" workers to go on strike.
The Sunday Telegraph claims several unions are offering tax-free payments through "strike funds".
The newspaper says Unite, which has threatened strikes in councils and across bus networks, has been putting up posters in local government buildings advertising its "£70 a day strike pay" to staff.
Meanwhile, almost half the people questioned in a new survey about the dispute think now is not the right time to strike.
The poll, commissioned by industry body the Rail Delivery Group, showed that while one in four supported the strike, two out of five were against.
Government 'pouring petrol on the fire'
Labour leader Sir Keir Starmer has criticised the government's handling of the dispute - claiming the Conservatives have been "pouring fuel on the fire".
During a speech in Warwick on Sunday, he will accuse Boris Johnson and Mr Shapps of actually wanting the strikes to go ahead, saying: "They want the country to grind to a halt so they can feed off the division."
"Instead of spending their time this week around the negotiating table, they are designing attack ads."
A Department for Transport spokesperson said the government has committed £16bn to keep the railways running throughout the pandemic.
They added: "The railway is still on life support, with passenger numbers 25% down and anything that drives away even more of them risks killing services and jobs.
"Train travel for millions more people is now a choice, not a necessity. Strikes stop our customers choosing rail, and they might never return."
In other developments that might irritate unions, The Sunday Times also claims the rail network is on the verge of closing all ticket offices at English stations.
According to the paper, plans have been drawn up to phase out paper tickets in a bid to save up to £500m a year.