Tens of thousands of appointments and operations are expected to be cancelled as a result of the 72-hour strike in England, which began on Monday morning.
More than 100,000 appointments have already been postponed this winter after nurses and other health workers took strike action in a dispute with the government over pay, according to NHS figures.
NHS leaders said that emergency care and other departments were under significant pressure, even with consultants and other staff taking on the work of junior doctors on picket lines.
The British Medical Association (BMA) says junior doctors’ pay has fallen in real terms by 26% since 2008/09 and reversing this would require a 35.3% pay rise.
On Friday, Health Secretary Steve Barclay invited the BMA to talks, but the union rejected the idea, saying there were "unacceptable" pre-conditions.
The pre-conditions are understood to have included looking at a non-consolidated lump sum payment for last year, whereas the BMA is seeking what it calls "full pay restoration".
The union has implored the government to drop the preconditions.
Dr Rob Laurenson and Dr Vivek Trivedi, co-chairs of the BMA’s junior doctor committee, said in a statement: "We remain open to entering talks with the government anytime and anywhere to bring this dispute to a swift resolution and restore the pay that junior doctors have lost.
"If the health secretary is truly committed to this, then he needs to drop these unreasonable pre-conditions and begin proper negotiations with us.
"The pre-conditions go against the very thing junior doctors are in dispute over. It begs the question; does he even understand why doctors are so angry?"
Junior doctors make up around 45% of the NHS’s medical workforce, and consultants and other medics have been drafted in to provide strike cover in areas such as A&E.
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Hospital bosses have said that they were planning services "hour by hour" during strike action and are diverting more senior doctors, who are not on strike, to the services in "greatest clinical need".
Professor Stephen Powis, medical director of NHS England, told BBC Radio 4’s Today programme on Monday the strikes are "likely to be the most severe of all those [strike] days this winter, perhaps even the most severe disruption that we’ve seen of any strike in the NHS during its history".
Matthew Taylor, chief executive of the NHS Confederation, said: "Leaders have worked hard to minimise disruption but with junior doctors making up nearly two fifths of an already understaffed workforce, thousands of appointments and non-urgent procedures have still needed to be cancelled so that the most life-critical services can be prioritised."
He added: "There are no winners in the current standoff between the BMA and the government. On behalf of our members and the communities they serve, we urge both sides of this dispute to compromise and bring these strikes to an end."
Talks between the government and other health unions - including those representing nurses, physiotherapists and ambulance workers - will continue this week, holding out hope of a breakthrough in the long-running NHS pay dispute.
On Monday, Mr Barclay said: "It is incredibly disappointing the British Medical Association has declined my offer to enter formal pay negotiations on the condition strikes are paused.
"I want to find a fair settlement which recognises the crucial role of junior doctors and the wider economic pressures facing the UK.
"I’ve been having constructive and meaningful talks with unions representing nurses, ambulance workers and other non-medical staff, which have agreed to pause strike action, and negotiations will continue this week."
It comes as members of several trade unions will strike on Budget day on Wednesday in what will be one of the biggest single days of industrial action for years.
Workers taking action include civil servants, teachers, university staff, London Underground drivers and BBC journalists.