Matt Hancock has blasted the thousands of people who fled London before Tier 4 restrictions came into force at midnight.
Train stations across the capital were packed with those trying to make a last minute escape to other parts of the country before Christmas.
Photographs and videos show packed platforms and waiting areas, with many services sold out.
The Health Secretary described the scenes as "totally irresponsible behaviour".
Mr Hancock, told Sky's Sophy Ridge on Sunday: "Especially in Tier 4 areas, everybody has to behave as if they might well have the virus."
He said: "This is deadly serious... This is a deadly disease, we've got to keep it under control and it's just been made more difficult by this new variant."
Mr Hancock has said the country faces an “enormous challenge” controlling the new strain of Covid-19 after scientists found it was able to spread more rapidly.
He suggested additional restrictions for England announced by the Prime Minister on Saturday may have to remain for “the next couple of months” while a vaccine is rolled out.
He added: “We know with this new variant you can catch it more easily from a small amount of the virus being present.
“All of the different measures we have in place, we need more of them to control the spread of the new variant than we did to control the spread of the old variant. That is the fundamental problem.
“We know that because we know that in November that in the areas where this new variant started, in Kent, the cases carried on rising whereas in the rest of the country the November lockdown worked very effectively.
“It is an enormous challenge, until we can get the vaccine rolled out to protect people. This is what we face over the next couple of months.”
The five-day Christmas bubble period has been reduced to just Christmas Day for England, Wales and Scotland - and scrapped completely for areas in England under new Tier 4 rules - but remains in Northern Ireland.
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