A further 20 million people in England will join the toughest tier of Covid-19 restrictions from Thursday.
The Midlands, North East, parts of the North West and parts of the South West are among those escalated to tier four.
And secondary schools across most of England are to remain closed for an extra two weeks for most pupils.
The public must “redouble” its efforts at this “critical moment”, the PM said, before adding he was confident things will be “very much better” by 5 April.
“All of these measures in the end are designed to save lives and protect the NHS,” he said at a Downing Street briefing. “For that very reason, I must ask you to follow the rules where you live tomorrow night and see in the new year safely at home.”
Earlier, the Oxford-AstraZeneca vaccine was approved for use in the UK, with the first doses to be given on Monday.
But Boris Johnson warned that people should not “in any way think that this is over” as “the virus is really surging”.
Some areas joining tier four include Leicester City, Coventry, Solihull, Swindon.
Leicestershire (Oadby and Wigston, Harborough, Hinckley and Bosworth, Blaby, Charnwood, North West Leicestershire, Melton)
Lincolnshire (City of Lincoln, Boston, South Kesteven, West Lindsey, North Kesteven, South Holland, East Lindsey) among many others.
His comments came as a further 50,023 new Covid cases were recorded in the UK on Wednesday, as well as 981 more deaths within 28 days of a positive test – more than double Tuesday’s total.
Under tier four rules, non-essential shops, beauty salons and hairdressers must close, and people are limited to meeting in a public outdoor place with their household, or one other person.
Health Secretary Matt Hancock told MPs that rising cases across England mean it is “therefore necessary to apply tier three measures more broadly too, including in Liverpool and North Yorkshire”.
In tier three areas, household mixing is banned indoors and in private gardens, while the rule of six applies in public spaces. Shops, gyms and personal care services can remain open, but hospitality settings must close except for takeaway.
All of the tier changes will come into effect at 00:01 GMT on Thursday, December 31.
Following his colleague in the Commons, Education Secretary Gavin Williamson said secondary schools across most of England will remain closed for an extra two weeks for most pupils.
He added that exam-year pupils will return a week earlier than their schoolmates in the week of 11 January, and in a small number of areas with the highest infection rates, primaries will remain closed temporarily.
Commenting on the delay, the prime minister said: “We must face the reality, the sheer pace of the spread of this new variant, requires us now to take even tougher action in some areas, and that does affect schools.”
Mr Johnson said that 60% of UK coronavirus cases were now the new, more transmissible, strain of Covid-19.
Asked by political editor Laura Kuenssberg if the government had been too slow to act, he said: “What we, unfortunately, were not able to budget for was this this new variant.”
He added: “It’s spreading rapidly from the places where it’s started, in the east of London and in Kent. And, alas, it’s starting to seed across the country.”
Meanwhile, a statement on behalf of nine council and other leaders in the north-east of England urged the government to replace its regional approach with a national lockdown “to ensure the spread of the new variant is slowed and efforts can be focused on the crucial roll-out of the vaccine”.
“This is a national problem and a national solution is required now,” they added.
Elsewhere in the UK, Wales and Northern Ireland are both in lockdown, as is mainland Scotland.
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