Under regulations to be brought forward imminently, providers of CQC-regulated activity - including GP practices, hospitals, and services delivering care in patients' homes - will only be allowed to employ staff in roles involving interaction with patients if they are fully vaccinated against COVID-19.
The regulations will cover not only frontline clinical staff, but also 'non-clinical workers not directly involved in patient care but who nevertheless may have direct, face to-face contact with patients, such as receptionists, ward clerks, porters and cleaners', guidance published by the government confirms.
Only a handful of staff will be exempt - including those aged under 18, those who are medically exempt, and those who do not have face-to-face contact with patients - such as staff providing remote care or management support 'in sites apart from patient areas'.
The decision comes just days before rules requiring staff working in care homes to be fully vaccinated - including GPs visiting patients - come into effect.
Announcing the decision in parliament, health and social care secretary Sajid Javid said the government had taken into account concerns that mandatory vaccination could further undermine an already-depleted NHS workforce.
He told MPs: 'Support for making vaccination a condition of deployment was tempered with concerns that some people may choose to leave their posts if we went ahead with this. I have concluded that the scales tip clearly to one side.
'Only those colleagues who can show that they are fully vaccinated against COVID-19 can be employed or engaged in those settings. There will be only two exceptions - for those who do not have face-to-face contact with patients and those who are exempt.
'These requirements will apply across health and wider social care settings that are regulated by the CQC. We are not the only country in the world that has taken such steps.
'We also consulted on flu vaccines, but having considered views that we should focus on COVID-19 we will not be introducing any requirements on flu jabs at this stage - but we will keep this under review.'
Official data show that 90% of NHS staff have now received at least two doses of COVID-19 vaccine, although in some NHS trusts coverage falls to around 80%.
Among staff working in care homes, numbers of staff who remain unvaccinated had more than halved to around 30,000 over the past month as the deadline for mandatory vaccination approached, the health and social care secretary said.
He said the decision to push back a vaccine mandate across health and social care as a whole to 1 April - 12 weeks after the new regulations are expected to be approved by parliament - was a recognition of the impact the move could have on the workforce.
Confirmation that COVID-19 vaccination will become mandatory comes after Mr Javid said last month he was 'leaning towards' the move.
A government consultation on making flu and COVID-19 vaccination mandatory for all frontline NHS staff closed on 22 October.
Three quarters of doctors at the BMA's annual conference earlier this year backed a motion that said all doctors should be vaccinated against COVID-19 - but doctors' leaders have also warned that mandatory jabs could further undermine an already-depleted NHS workforce, with potentially 'devastating' consequences through winter.
BMA polling suggests the vast majority of doctors are already double-vaccinated.