Letters and texts will be sent out in the next few days urging people with serious medical conditions to stay indoors.
Prime Minister Boris Johnson has called on the public to join a "collective national effort" and follow social distancing guidance.
The number of people who have died in the UK with coronavirus rose to 233 on Saturday, as cases topped 5,000.
People who are most at risk will receive letters or text messages strongly advising them not to go out for 12 weeks to protect themselves, the government said.
They include people who have received organ transplants, are living with severe respiratory conditions such as cystic fibrosis or specific cancers, such as blood or bone marrow.
In a message to the country on Saturday evening, Mr Johnson said: "The numbers are very stark, and they are accelerating.
He said the UK is only "two or three" weeks behind Italy, adding that he recognised the government was imposing measures "never seen before either in peace or war" - but said they were essential.
Italy has seen its death toll for the past month reach 4,825, the highest in the world – and yesterday there were nearly 800 deaths in one day in the country.
It comes after the government this week told all restaurants, cafes and pubs - as well as some other public spaces like gyms and cinemas - to close.
Elsewhere, Mayor of London Sadiq Khan echoed the PM's call for social distancing.
Appealing to the public, he said: "Don't leave home unless you have to, don't use public transport unless essential… do it for loved ones who will die if you don't."
Under emergency legislation going through Parliament next week, airports could be shut and people held on public health grounds, while immigration officials could place people in isolation.
Similar moves have been announced in countries around the globe.