Boris Johnson described the new league, which includes six leading English clubs, as “ludicrous”.
The 12 founding members of the league face a fierce backlash after unveiling proposals for a breakaway tournament.
One insisted they were doing it to “save football”.
Real Madrid President Florentino Perez said the decision to create the new league, which his club would be a part of, was in part taken because “young people are no longer interested” in the game.
He told a Spanish TV show: “Audiences are decreasing and rights are decreasing and something had to be done. We are all ruined. Television has to change so we can adapt.”
The 14 Premier League clubs not participating in the new venture are also due to discuss their response later.
Fans and pundits have expressed fury at what they say would be an unfair competition that would lock many teams out of top European football.
The proposed league – which has been described as a football “closed shop” by a government minister – has united MPs from every party against it.
Under the plans – revealed on Sunday – the 12 founding football clubs would be permanent members and never face relegation.
Critics say the new league could supplant the existing Champions League and disrupt the current football “pyramid” that sees teams rise or fall on merit.
Writing in the Sun, the prime minister said he was “horrified” at the implications for clubs across the country.
In a direct message to fans, he said: “It is your game – and you can rest assured that I’m going to do everything I can to give this ludicrous plan a straight red.”
Labour’s shadow sports minister Alison McGovern urged the UK’s competitions watchdog to investigate, describing the plans as “nothing short of an attempt to stitch up competition for a few elite clubs at the top”.
And on Monday, the Duke of Cambridge, who is president of the Football Association, said he shared fans’ concerns about “the damage it risks causing to the game we love”.
Sky Sports confirmed it had not “not been involved in any discussions” about the breakaway league.
“We are completely focused on supporting our long term football partners in the UK and in Europe,” the broadcaster said.