Communities Secretary Robert Jenrick revealed the latest measures today in an hour-long press conference in Number 10 Downing Street.
He said 1.5m people in the UK will be written to by the health service telling them they must now stay in their homes for 12 weeks, not even leaving to buy food.
He said: “In recent weeks heroic workers in the NHS, social care and public services in local government have been shouldering the country’s burden.
“I think we owe it to them and the most vulnerable in society to stay home, to protect the NHS and, by doing this, to save lives.
“And so today we have to go further to shield the most clinically vulnerable people to help save their lives.”
Those who have received organ transplants, are living with severe respiratory conditions such as cystic fibrosis and severe chronic bronchitis (COPD), or specific cancers like of the blood or bone marrow will now have to stay inside for 12 weeks.
Some of those receiving certain types of drug treatments including ones which suppress the immune system – leaving the body less able to fight off the virus - will also be subject to the measures.
Free food deliveries will be organised for those stuck inside, as well as medications being brought to their homes.
But Mr Jenrick said: “I don’t underestimate what we’re asking of people. It will be tough.
“But if you are one of these people I want to assure these people on behalf of the Government that you are not alone.”
Groceries would be delivered by councils working with supermarkets, with “parcels left on the doorstep”.
“Nobody needs to worry about getting the food and essential items that they will need.”
He said there would be opportunities for members of the public to volunteer.
The announcement comes amid concern the wider public was not adhering to advice to stay away from others.
The Prime Minister gave what appeared to be a last chance warning to members of the public who had been floating social distancing rules, warning current advice was “absolutely crucial” as he added: “We will bring forward further measures if we think that is necessary.”
He said: “I don’t think you need to use your imagination very much to see where we might have to go, and we will think about this very very actively in the next 24 hours.”
The measures introduced today and previously are designed both to save lives but also to ease the acute pressure felt by the NHS in tackling the virus.
Mr Johnson - who has faced criticism for not acting faster to slow the spread of the virus - said ministers had already closed down whole swathes of the economy, shutting pubs, clubs and restaurants.
He said the Government had always followed the scientific advice when it came to access to open spaces - but warned people needed to observe the guidance that they should not gather in groups and remain two metres apart.
"What they have always said so far is that the health benefits for the whole of society of keeping the parks and playgrounds open if we possibly can outweigh the epidemiological value of closing them," he said.
"But of course looking at the way people behave and the way they are responding, we keep that under constant, constant review.
"If people can't make use of parks and playgrounds responsibly, if they can't do it in a way that observes the two-metre rule then of course we are going to have to look at further measures.
"The general principle should be that we should all as far as we possibly can stay home, protect our NHS and thereby save lives."