From midnight, the country was split into three COVID-19 alert levels - "medium", "high" and "very high" - but the prime minister is already under growing pressure to take even further action.
Labour leader Sir Keir Starmer is now demanding that Boris Johnson puts England into a two to three-week "circuit breaker" lockdown to coincide with October half-term - with the support of the Liberal Democrats.
But speaking to Kay Burley, Work and Pensions Secretary Therese Coffey said: "I do not believe that the prime minister wants to set off on a national lockdown, but as ever he is advised by scientists - he takes that decision."
Asked if England was heading for a national lockdown in the next two weeks, Coffey said: "I don't believe that is the case but as I say this will continue to be a decision that the prime minister will lead on."
She added that "we have the three tiers and we need to make sure we give that the chance to work", and another national lockdown would be "not really fair"
Liverpool City Region is in the top tier, with bars and pubs forced to shut if they cannot operate as restaurants. Residents have also been banned from socialising with other households indoors and outdoors, including in private gardens.
Last night, videos on social media showed groups of people enjoying a final night out in the city before the new restrictions came into force - with Merseyside Police confirming to Sky News that a "large crowd" had to be dispersed.
Discussions are going to be held on whether Greater Manchester and Lancashire should be reclassified to also join the top tier of restrictions, amid concern at rising coronavirus infection rates across the North West.
Ahead of those talks, Greater Manchester Mayor Andy Burnham accused the government of "piling the pressure on" without providing an adequate package of economic support.
He claimed the possible reclassification of the region "risks confusing people" so soon after Greater Manchester was placed in Tier 2 of the new system of localised restrictions.
Mr Johnson saw MPs approve the new three-tier system on Tuesday night, but he was also hit with a dual challenge from both Labour and his own Conservative MPs.
Sir Keir said a short national lockdown would "break the cycle" of COVID-19 transmission across the country.
Shadow Cabinet Office minister Rachel Reeves told Sky News that it was "not too late for the government to change course".
"I plead with the prime minister to listen to the scientists and get on the right path to control this virus, protect the NHS and save lives," she said.
A four-week "circuit breaker" lockdown will come into force in Northern Ireland on Friday in an attempt to stall the rise in coronavirus infections.
Welsh First Minister Mark Drakeford has told Sky News he is is carrying out "detailed planning" for a potential short national lockdown.
Mr Johnson will face Sir Keir in the House of Commons during Prime Minister's Questions later, when the Labour leader will likely accuse the government of failing to follow the recommendations of scientists for nationwide action.
Two members of the Scientific Advisory Group for Emergencies (SAGE) are due to release a joint paper that suggests thousands of COVID-19 deaths could be avoided before Christmas if a circuit breaker lockdown is imposed over half-term.
Another SAGE member, Sir Jeremy Farrar - director of the Wellcome Trust - described the government's current strategy of enhanced localised measures as the "worst of all worlds" as it offers "the economic damage of more restrictions without the gain of a reduction in transmission".
In a sign of Downing Street's anger at Sir Keir over his call for greater action, a senior government source branded the Labour leader a "shameless opportunist" and accused him of "playing political games in the middle of a global pandemic".
But while the prime minister is now facing a more hostile opposition to his handling of the coronavirus crisis, Mr Johnson has also been delivered a warning shot by his own Tory backbenchers.
A total of 44 Conservative MPs opposed the 10pm curfew for pubs and restaurants in England in a House of Commons vote on Tuesday night - the biggest Tory rebellion that Mr Johnson has faced since he became prime minister.
The rebel group included Bolton West MP Chris Green, who quit as a junior ministerial aide minutes before the vote.
In his resignation letter to the prime minister, Mr Green said the local lockdown in his constituency had failed and "the attempted cure is worse than the disease".
Mr Johnson had addressed Conservative backbenchers via Zoom before Tuesday's vote.
It was reported that the prime minister used the video call to joke that many people would welcome the "rule of six" for social gatherings as they will be able to avoid their in-laws at Christmas.
"Les Dawson heading up the COVID-19 response was not the 2020 I was expecting," said Labour shadow minister Jess Phillips in her condemnation of Mr Johnson's reported remarks.