FIFA president Gianni Infantino has said his organisation "strongly disapproves" of plans for a European Super League and has warned the breakaway clubs they will have to "live with the consequences of their choice".
Twelve clubs - including the Premier League's so-called 'big six' - are part of proposals which would fundamentally alter the shape of European football.
Infantino told the UEFA Congress on Tuesday morning: "We can only strongly disapprove the creation of the Super League, a Super League which is a closed shop, which is a breakaway from the current institutions, from the leagues, from the associations, from UEFA and from FIFA.
"There is a lot to throw away for the short-term financial gain of some. They need to reflect, and they need to assume responsibility."
He warned the breakaway clubs: "If some elect to go their own way then they must live with the consequences of their choice. They are responsible for their choice.
"Concretely, this means either you're in or you're out. You cannot be half in or half out."
It is understood the Premier League has called its other 14 clubs to an emergency shareholders' meeting on Tuesday morning, to which the 'big six' - Arsenal, Chelsea, Liverpool, Manchester City, Manchester United and Tottenham - have not been invited.
The other clubs who have signed for the Super League are Barcelona, Real Madrid, Atletico Madrid, Juventus, and the two Milan clubs Inter and AC.
Earlier, condemnation of the 12 rebels clubs from England, Spain and Italy even came from Prince William, who followed the British government in railing against moves to split from longstanding structures to play in a largely closed competition rather than Europe's existing UEFA-run Champions League.
UEFA President Aleksander Ceferin turned on club leaders he called "snakes" and "liars," singling out Juventus chairman Andrea Agnelli and Manchester United vice-chairman Ed Woodward for betraying him by reneging on a pledge to stick within existing structures.
Ceferin threatened players from the Super League clubs with being banned from the European Championship and next year's World Cup.
"They will not be able to represent their national teams at any matches," Ceferin warned earlier.
"UEFA and the footballing world stand united against the disgraceful self-serving proposal we have seen in the last 24 hours from a select few clubs in Europe that are fuelled purely by greed above all else."
Ceferin said he wants to boot them out as "as soon as possible" from UEFA competitions, but that will require "legal assessments" that will begin on Tuesday morning.
However, Real Madrid president Florentino Perez, the founding chairman of the Super League, downplayed UEFA's threat to ban players.
The players "can be assured that this won't happen," Perez said in a late-night Spanish television interview.
"It's not going to happen. We won't get into the legal aspects of it, but it won't happen. It's impossible."
The 12 clubs planning to start the breakaway Super League wrote to the leaders of FIFA and UEFA that they have begun legal action aimed at fending off threats to block their competition.
Perez said the new league likely won't start next season if no deal is reached with European soccer's governing body.
He also didn't completely rule out the possibility that the new league won't get started at all, but indicated that the clubs were prepared to go all the way to make it happen - underwritten by funding of 4.5 billion euros from American bank JPMorgan Chase.