Norfolk is set to remain under Tier 4 restrictions as millions more people across England join the toughest tier from Thursday.
Matt Hancock told the House of Commons that sharply rising cases and the hospitalisations that follow “demonstrate the need to act where the virus is spreading”.
He said the majority of new cases are believed to be the new variant, which is now spreading across most of England, with cases doubling fast.
It comes as University of East Anglia infectious diseases expert Prof Paul Hunter warned a national coronavirus lockdown is "inevitable".
The country faces a "really difficult six months" because failures to combat the pandemic contributed to the emergence of the new Covid-10 variant, he said.
The health secretary said it was necessary to apply Tier 4 measures to a wider area including the remaining parts of the South East, as well as large parts of the Midlands, north-east and south-west England.
Tier 4 will also be expanded to cover much of Norfolk’s neighbouring county Lincolnshire, including Lincoln, Boston, South Kesteven, West Lindsey, North Kesteven, South Holland and East Lindsey.
An additional 20 million people will be in Tier 4 from December 31 bringing the total to 44 million or 78pc of the population of England.
Under Tier 4 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.
Tier 3 restrictions are also being expanded to Liverpool and North Yorkshire.
The changes come into effect after midnight.
The health secretary said: "The new variant means that three quarters of the population are now going to be in Tier 4 and almost all of the country in Tiers 3 and 4.
"And I know that Tier 3 and 4 measures place a significant burden on people, and especially on businesses affected, but I am afraid it is absolutely necessary because of the number of cases that we've seen.
"But where we are still able to give places greater freedoms, we will continue to do so."
Earlier, the Oxford-AstraZeneca vaccine was approved for use in the UK, with the first 530,000 doses available from Monday. The vaccine will give people protection against Covid-19 after the first dose.
Mr Hancock said that the Oxford vaccine means the day on which restrictions are lifted can be brought forward.
He told MPs: "It brings forward the day on which we can lift the restrictions that no-one in this House wants to see any longer than are absolutely necessary.
"But we must act to suppress the virus now, not least because the new variant makes the time between now and then even more difficult.
"And so whilst we have the good news of the vaccine today, we also have to take some difficult decisions."
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