Junior doctors -- those below consultant level -- join picket lines from 0700 GMT to the same time on Saturday in a major escalation of their long-running pay dispute.
Six more days of industrial action are planned from January 3.
The strike comes at one of the busiest times of the year for the state-funded National Health Service (NHS), as it faces increased pressure from seasonal respiratory illnesses.
The strike has drawn criticsm from UK Prime Minister Rishi Sunak and hospital leaders who have described the lengthy walkout as their "worst fears realised".
"We would encourage junior doctors to consider carefully the extremely significant impact striking at such a challenging time will have both on the NHS and for individual patients and to return to talks," Sunak said on Tuesday.
The British Medical Association (BMA) announced the strike earlier this month after a breakdown in talks with the government.
The union said junior doctors have been offered a 3.0-percent rise on top of the average 8.8-percent increase they were given earlier this year.
It rejected the offer because the cash would be split unevenly across different doctor grades and would "still amount to pay cuts for many doctors".
Health policy is a devolved matter for the administrations in Scotland, Wales and Northern Ireland, with the UK government overseeing England.
Junior doctors in Wales are due to walk out for 72 hours from January 15. Those in Northern Ireland are being balloted for potential strike action.
Their Scottish counterparts have struck a deal with the government in Edinburgh.
The NHS typically sees a rise in the number of people in hospital in the two weeks after Christmas due to people delaying seeking treatment in order to spend the festive season with loved ones.
NHS England's national medical director Stephen Powis warned that the strike would cause "huge disruption" and "put the NHS on the back foot" as it enters its most pressurised time of year.
The service is already facing huge backlogs in waiting times for appointments and surgery, blamed on treatment postponement during Covid but also years of under-funding.
