FIFA boss Gianni Infantino "strongly disapproves" of the breakaway European Super League and says the 12 clubs will have to "live with the consequences" of their decision to join.
Premier League clubs Arsenal, Chelsea, Liverpool, Manchester City, Manchester United and Tottenham are part of the proposed league.
"There is a lot to throw away for maybe a short-term financial gain for some," said Infantino.
"Either you are in or you are out."
Meanwhile, UK Prime Minister Boris Johnson met with the Football Association, Premier League officials and fans' representatives on Tuesday, after which the government said it will take "whatever action necessary", including legislative options, to ensure the proposals were stopped.
Downing Street added: "No action is off the table."
In other developments:
Uefa president Aleksander Ceferin called on the English clubs to "come to your senses" Everton criticised the "preposterous arrogance" of the clubs involved Real Madrid president Florentino Perez said that the new league was needed to "save football"The proposed tournament would see teams play one another in midweek games in an attempt to have more matches between the big-name clubs.
The other clubs involved are AC Milan, Atletico Madrid, Barcelona, Inter Milan, Juventus and Real Madrid.
The plans have been heavily criticised by fans, pundits, football's governing bodies and members of the UK government.
"It is our task to protect the European sport model. If some elect to go their own way, they must live with the consequences of their choices," said Infantino, the president of world football's governing body.
"They are responsible for their choice completely. This means you are either in or you are out. You cannot be half in and half out."
There have been protests outside the grounds of the Premier League clubs who have signed up to the league.
Leeds players also wore T-shirts saying 'Earn it' next to the Champions League logo and 'Football is for the fans' before their 1-1 draw with Liverpool on Monday.
On Tuesday, Uefa president Ceferin called on the English clubs to "come to your senses".
Directly addressing the owners of the six Premier League clubs, he said: "Gentlemen, you made a huge mistake. There is time to change your mind.
"Come to your senses. Not out of love for football - I don't imagine you have much of that - but out of respect for the people who bleed for the team, out of respect for the home of football. I know we are right and they are wrong. It is a match we cannot lose."
The president of the German Football Association (DFB) has said that the 12 clubs should be banned from all competitions.
No German club has signed up to the ESL.
"Football is open and it is there for everyone. A closed Super League on the other hand is only for the super rich and the super ruthless," Fritz Keller said.
Everton and Brighton released statements on Tuesday criticising their fellow Premier League clubs for joining.
In a lengthy statement, the Everton board said the six clubs were "tarnishing the reputation of our league and the game", accused them of "disrespect" towards fellow Premier League clubs and said they were "taking for granted and even betraying the majority of football supporters across our country and beyond".
The statement added: "This preposterous arrogance is not wanted anywhere in football outside of the clubs that have drafted this plan.
"On behalf of everyone associated with Everton, we respectfully ask that the proposals are immediately withdrawn and that the private meetings and subversive practises that have brought our beautiful game to possibly its lowest ever position in terms of trust end now."
The 14 Premier League clubs not signed up to the ESL will meet on Tuesday to assess the proposals and consider a response.
Real Madrid president Florentino Perez said that the new league was needed to "save football" and help recoup losses caused by the coronavirus pandemic.
However, Everton have accused the six Premier League clubs of acting "entirely in their own interests".
They added: "At this time of national and international crisis - and a defining period for our game - clubs should be working together collaboratively with the ideals of our game and its supporters uppermost.
"Instead, these clubs have been secretly conspiring to break away from a football pyramid that has served them so well.
"The self-proclaimed Super Six appear intent on disenfranchising supporters across the game - including their own - by putting the very structure that underpins the game we love under threat."
Brighton said the breakaway league showed "a clear lack of respect" for other sides, adding that it would "destroy the dreams of clubs at every level".
The statement said: "These plans are the latest in an alarming and growing list of clandestine attempts from a small group of clubs whose actions would be wiping out close to 150 years of football's tradition."
Burnley have called on the government to introduce an independent regulator to protect English football through legislation.
Fifa said in January that players involved in a breakaway league would be barred from international competitions.
Agent Jonathan Barnett, who represents Wales and Tottenham forward Gareth Bale, said he would go to court if such a ban was introduced.
"The only people who are really going to suffer inside the business is players," Barnett told Radio 4's Today programme.
"I've been speaking to Fifpro [the players' union] and I assure you, we will go to court to fight the rights of the players."
Source: BBC