Last-ditch talks failed to resolve the bitter dispute over pay, jobs and conditions, with all sides blaming each other for the lack of progress.
Much of Britain will have no passenger trains for the entire day today.
Services will primarily be restricted to main lines, but even those will only be open between 7.30am and 6.30pm.
Thousands of members of the Rail, Maritime and Transport (RMT) union at Network Rail and 13 train operators will walk out today, Thursday and Saturday.
Those operators not involved in the industrial action will still suffer from disruption due to Network Rail signallers going on strike.
London Underground workers will also walk out today.
Unions have reacted with fury to reports Labour has banned its frontbenchers from picket lines, in a leaked memo.
Sharon Graham, general secretary of Unite, told the PA news agency: "The Labour Party was founded by the trade unions and we expect Labour MPs to defend workers, by words and by actions.”
This week's strikes will cause travel misery for millions.
Pupils and parents who normally use trains are being urged to make an alternative plan for getting to school for A-level and GCSE exams.
And motorists are being warned to expect a surge in traffic as train passengers switch to the roads.
Prime Minister Boris Johnson is expected to say ahead of a Cabinet meeting today that unions are “harming the very people they claim to be helping”.
He is set to accuse unions of “driving away commuters who ultimately support the jobs of rail workers”, while also hitting businesses across the country.
He will say: “Too high demands on pay will also make it incredibly difficult to bring to an end the current challenges facing families around the world with rising costs of living.
“Now is the time to come to a sensible compromise for the good of the British people and the rail workforce.”
RMT general secretary Mick Lynch said Network Rail had offered a two per cent pay rise with the possibility of a further one per cent later dependent on efficiency savings.
He told BBC's Newsnight that Network Rail had “escalated” the dispute during yesterday’s talks, saying: “They have issued me a letter saying that there are going to be redundancies starting from July 1.
“So rather than trying to come to an agreement in this dispute, they've escalated it by giving us formal notice of redundancy amongst our Network Rail members.”
He warned the dispute could continue for months.
Sheffield’s main operators, Northern, East Midlands and Transpennine Express, have released timetables detailing their limited services during the strikes days on Tuesday, June 21, Thursday, June 23, and Saturday, June 25.
Services between strike days will operate at a reduced rate of 60 per cent.
Train users are being urged to find alternative ways to travel during the strike.