Boris Johnson has said the government will do everything it can to make sure the new European Super League "doesn't go ahead in the way that it's currently being proposed", calling the plans "very damaging for football", Sky News reported.
The prime minister said he would work with football authorities opposed to the move, adding: "I don't think that it's good news for fans, I don't think it's good news for football in this country."
He said: "These clubs are not just great global brands - of course they're great global brands - they're also clubs that have originated historically from their towns, from their cities, from their local communities, they should have a link with those fans, and with the fan base in their community."
Mr Johnson said the six Premier League clubs involved "must answer to their fans" before deciding to launch the breakaway competition.
Twelve of Europe's leading football clubs have agreed to establish a Super League, despite widespread criticism of the plans from fans, former footballers, managers, and the football authorities.
A statement from the new competition said: "AC Milan, Arsenal, Atlético Madrid, Chelsea, Barcelona, Inter Milan, Juventus, Liverpool, Manchester City, Manchester United, Real Madrid and Tottenham Hotspur have all joined as founding clubs.
"It is anticipated that a further three clubs will join ahead of the inaugural season, which is intended to commence as soon as practicable."
Florentino Pérez, president of Real Madrid and the first chairman of the Super League, said: "We will help football at every level and take it to its rightful place in the world.
"Football is the only global sport in the world with more than four billion fans and our responsibility as big clubs is to respond to their desires."
The project is being launched to rival Uefa's Champions League format which currently dominates European football - and the announcement came a day before Uefa was due to sign off on plans for an expanded and restructured tournament.
The new Super League has been criticised by politicians including Mr Johnson and Labour Party leader Sir Keir Starmer, as well as former players such as Gary Neville.
Sir Keir said the plans had ignored the fans, adding: "Football in empty stadiums hasn't been the same over the last year. I can't wait to get back to games. But this proposal risks shutting the door on fans for good, reducing them to mere spectators and consumers.
"The clubs involved in this proposal should rethink immediately. And if they don't, they should face the consequences of their actions. Because football without fans is nothing."
Former Manchester United defender Gary Neville told Sky Sports: "I'm not against the modernisation of football competitions, we have the Premier League, the Champions League, but I think to bring forward proposals in the midst of Covid and the economic crisis for all clubs is an absolute scandal.
"United and the rest of the 'Big Six' that have signed up to it against the rest of the Premier League should be ashamed of themselves."
Neville added: "They should deduct six points off all six teams that have signed up to it. Deduct points off them all. To do it during a season? It's a joke."
Uefa, the FA, and the Premier League are among others to have expressed opposition, saying in a joint statement that they "remain united in our efforts to stop this cynical project", adding: "We thank those clubs in other countries, especially the French and German clubs, who have refused to sign up to this.
"This persistent self-interest of a few has been going on for too long. Enough is enough."
The English FA said: "We would not provide permission to any competition that would be damaging to English football, and will take any legal and/or regulatory action necessary to protect the broader interests of the game."
The Super League competition will see 20 participating clubs - 15 founding clubs and a further five teams able to qualify annually based on their achievements during the previous season.
The Super League will begin in August with clubs participating in two groups of 10, playing home and away fixtures, some during the week, with the top three in each group qualifying for the quarter-finals.
Teams finishing fourth and fifth will compete in a two-legged play-off for the remaining quarter-final spots before a knockout format is used to reach the final at the end of May, which will be staged as a single fixture at a neutral venue.
In exchange for their commitment, founding clubs will receive an amount of €3.5bn (£3bn) to "support their infrastructure investment plans and to offset the impact of the Covid pandemic", the league's statement said.
Club players will be able to continue competing in their national leagues and, as soon as possible after the men's competition begins, a women's league will also be launched.