UK nationals and residents returning to Britain from "red list" countries will be forced to quarantine for 10 days in government-provided accommodation such as hotels, Boris Johnson has announced.
The prime minister said people will be met at the airport and transported to a local hotel, where they must complete their period of self-isolation.
Home Secretary Priti Patel, providing further detail on the policy, said there will be no exceptions to the rule and anyone attempting to exit isolation early will be fined.
The new law is designed to improve compliance with self-isolation rules in order to reduce the risk of new variants of coronavirus being brought to the UK.
Priti Patel outlines new mandatory quarantine rules for some arrivals into the UK
Ms Patel said "too many" people are still entering the UK, despite lockdowns being in place across all four nations.
Mr Johnson pointed out that foreign nationals from 22 countries where new variants have been identified - including South Africa, Portugal and South American nations - are not allowed entry to the UK.
He added: "In order to reduce the risk posed by UK nationals and residents returning home from these countries, I can announce that we will require all such arrivals who cannot be refused entry to isolate in government provided accommodation, such as hotels, for 10 days without exception.
"They will be met at the airport and transported directly into quarantine. The Department of Health and Social Care is working to establish these facilities as quickly as possible."
Speaking in the Commons after the PM, Ms Patel said: "[Arrivals] will be required to isolate for 10 days without exception and the Department for Health and Social Care will set out further details on this approach next week."
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She added: "Going on holiday is not a valid reason, so we will introduce a new requirement so that people wishing to travel must first make a declaration as to why they need to travel.
"This reason for travel will be checked by carriers prior to departure and this approach effectively mirrors the checks on arrivals that are already in place with the passenger locator form."
It is hoped the law will protect the UK against the import of new variants, some of which are thought to be more deadly than the original strain, with it not yet certain what impact the mutants could have on the vaccine rollout.
Ms Patel said the measures will "reduce passenger flow so that only a small number of people for whom it is absolutely essential to travel are doing so and therefore reducing the risk to our world-leading vaccine programme".
While there is no evidence the new strains are resistant to vaccines being used in the UK, ministers are keen to minimise the risk they pose by enforcing the new rule.
Labour's shadow home secretary Nick Thomas-Symonds said the government's plans for hotel quarantining did not go far enough.
He said: "Mutations of the virus risk undermining the efficacy of the vaccines, threatening life and hope.
"We cannot know where these mutations will emerge from next and the truth is the Government is once again behind the curve.
"Labour is calling for a comprehensive hotel quarantining. Today's announcement is too limited, it leaves huge gaps in our defences against emerging strains.
"We know that the strains that emerged in South Africa and Brazil have already reached these shores. Little wonder really when controls have been so lax."
The Welsh government also said the new UK-wide quarantine restrictions needed to be broadened out.
A Welsh Government spokesperson said: "We have agreed on the need for a joint approach between the four nations of the UK and the Republic of Ireland to strengthen border health measures in order to prevent the further spread of coronavirus.
"However, we do not believe the approach as set out by the UK Government goes far enough. Further discussions on the details of the proposals will take place as soon as possible."
On Friday, Prime Minister Johnson warned new variants of coronavirus may be more deadly than the original strain of the virus, prompting calls for mandatory hotel quarantine to be imposed.
It comes after the UK's official coronavirus death toll passed the grim milestone of 100,000.
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Shadow health secretary Jonathan Ashworth criticised the government for failing to impose strict measures at the borders soon enough.
Speaking on BBC Breakfast, he said: "We should have had comprehensive border controls in for the past year.
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"Priti Patel and Boris Johnson, they tell us they want to take control of their borders, but the one time it actually mattered, and they needed to take control of our borders to protect us, they failed.
"I would urge the government to look at a comprehensive policy, not just the hotspots, because remember, there will be areas or countries across the world where there are mutations which haven't been identified yet because they don't have the same level of scientific ability."
Northern Ireland's First Minister Arlene Foster said a four-nations approach to the issue was being taken, while the Welsh Government said it expects to discuss the plans with Westminster.
In Scotland, Deputy First Minister John Swinney said the Scottish Government would "go at least as far" as England in enhancing quarantine arrangements.