Matt Hancock has announced new restrictions for Liverpool, Warrington and Middlesbrough in a bid to curb rising coronavirus infections.
Households will be banned from mixing in all social settings except for in parks and outside pubs, cafes and restaurants.
Residents are advised only to visit care homes in “exceptional circumstances”, and to only use public transport for essential journeys, which include going to work and school.
“I understand how much of an imposition this is," the health secretary said. “I want rules like this to stay in place for as short a time as possible.”
Liverpool’s metro mayor Steve Rotherham had earlier described the looming new measures as likely “more draconian” than those introduced just last week, and likely to carry an “emotional impact”.
But the government “has to do something”, he said, warning that “all of our figures are going badly in the wrong direction”.
In Liverpool, 1,287 new coronavirus cases were recorded in the seven days up to September 27, the equivalent of 258.4 cases per 100,000 people.
Despite Merseyside having already been subject to additional local restrictions, the city's rate is the third highest in the country. Neighbouring borough Knowsley has the second highest rate, with 261.8 cases per 100,000.
Politicians in the region are reported to have met with the health secretary on Wednesday evening, with a final decision taken at a meeting chaired by Boris Johnson on Thursday morning.
City leaders were waiting to be informed of ministers’ decisions ahead of Mr Hancock’s speech in the Commons, but had expected the new rules to be largely similar to those introduced in the North East.
In a joint statement, Mr Rotheram and the leaders of Liverpool, Sefton, Wirral, St Helens, Halton and Knowsley authorities have called for the government to work with them, provide financial support and increase testing capacity.
“Throughout the pandemic, we have always put the health of our residents first and we will continue to do everything we can to stop the spread of coronavirus and keep as many people as possible safe,” they said.
“However, at the same time, we must be clear that any further restrictions will deal a hammer blow to our economy.”
Announcing the new measures, the health secretary also pledged £7m in funding to assist the affected areas.
The stricter measures come just nine days after initial local curbs - which are still in effect - were introduced in Merseyside, Warrington, Halton and Lancashire.
These included a ban on different households mixing in private homes and gardens, save for those in social bubbles, and guidance to use public transport only for essential purposes.
The new rules announced on Thursday come as a study based on the testing of 80,000 volunteers across England suggested the increased local restrictions in northwest and northeast England were successfully driving down new infections.
“We've seen the doubling time - from the last time we did the survey to now - has reduced to about 10 days ... from seven to eight days, so that has been slowing,” React study director Paul Elliott told the BBC’s Today programme.
“At the moment, we seem to be still at very high levels of the virus, and we do seem to still have a bit of an upward trajectory, but that very fast increase in the virus seems to have slowed and that's very encouraging,” he added.
Some 55 people per 10,000 tested positive in the study, which was carried out between 18 and 26 September, suggesting 411,000 people in England have the virus.
Additional reporting by PA