Plans to phase out the sale of cigarettes in England would be the "biggest public health intervention in a generation", Rishi Sunak has said.
The PM told the BBC there was "no safe level of smoking" when asked about restricting people's right to choose.
His plan seeks to raise the legal age of smoking every year by a year so that eventually no-one can buy tobacco.
Tory MPs will be allowed a free vote while Labour indicated it would back the policy.
But some critics of the policy say it could lead to the creation of a "black market".
Making the announcement in his keynote speech at the Conservative Party Conference, Mr Sunak said he believed it was the right step to tackle the leading cause of preventable ill-health.
In an interview with Radio 4's Today programme, Mr Sunak was challenged on why he was taking measures to ban the future sale of cigarettes but in June pushed back part of the government's anti-obesity strategy, saying he believed in "people's right to choose".
Originally scheduled for this month, plans to ban two-for-one junk food deals have been delayed by the government for another two years.
But Mr Sunak told the BBC smoking cigarettes was not the same as eating crisps or a piece of cake because it could not be part of a balanced diet and there was no safe level of smoking.
"Smoking is unequivocally the single biggest preventable cause of death, disability and illness in our society," he said.
"Everyone recognises this measure will be the single biggest intervention in public health in a generation."
He said measures to restrict choice were "never easy" but nobody would want their children or grandchildren to grow up to smoke.
Smoking increases the risk of strokes, heart disease, dementia and stillbirth as well as causing one in four deaths from cancer.
Smoking rates have been falling since the 1970s. But there are still more than five million smokers in England and six million across the UK.
Currently, one in nine 18 to 24-year-olds smokes, according to the Office for National Statistics.
The idea of gradually increasing the smoking age was put forward last year by Javed Khan, the former Barnardo's chief executive, who was asked by ministers to consider new approaches to tackling smoking.
At the time, the government, which was led by Boris Johnson, said such a move was unlikely.
But Mr Sunak has decided to throw his backing behind it as a way of meeting the government's ambition for England to be smokefree by 2030 - defined as less than 5% of the population smoking.
Labour said it would "not play politics with public health" and would lend the prime minister the votes to get the law passed - but the plan is likely to meet opposition from the libertarian wing of the Conservative Party.
Earlier this week, former prime minister Liz Truss said the party needed to "stop banning things". It is understood she will not vote in favour of the policy.
Christopher Snowdon, head of Lifestyle Economics at the Institute of Economic Affairs think tank, told the BBC the policy if implemented would lead to "massive black markets".
"You're going to have, almost certainly, a fairly large, informal market of smokers who are old enough to buy cigarettes selling cigarettes to people who are not old enough.
"The problem with prohibition isn't that it doesn't have any effect whatsoever on consumption, the problem with prohibition is it leads to massive black markets and a lot of tax revenues gone."
Simon Clark, director of the smokers' rights group Forest, accused the prime minister of "dumbing down" by treating future generations of adults like children.
He added that Mr Sunak had taken a "wrecking ball to the principles of choice and personal responsibility".
But Cancer Research UK's Michelle Mitchell said the announcement on the smoking age was a "critical step".
"If implemented, the prime minister will deserve great credit for putting the health of UK citizens ahead of the interests of the tobacco lobby."
Deborah Arnott, from campaign group Action on Smoking and Health (ASH), said what had been announced was an "unprecedented" set of measures which would hasten the day smoking is obsolete.
Also in his interview with the Today programme, Mr Sunak:
- Did not directly answer whether he agreed with Home Secretary Suella Braverman who said immigration posed an "existential threat to the West's way of life" and warning of an "invasion" and hurricane" - Mr Sunak said it was putting unsustainable pressure on the UK
- Said the global investors he has spoken to were not concerned about the scrapping of the HS2 northern leg
While Mr Sunak undoubtedly hopes his plans to phase out smoking will be a legacy of his time in office, his first conference as PM was overshadowed by his decision, and the speculation in the days leading up to it, to axe the northern leg of the HS2 rail project.
While critics reacted with anger to the decision, the PM insisted investments would instead be made in transport projects across the country.
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