FIFA president Gianni Infantino condemned the European Super League as he warned clubs involved they "cannot be half in or half out" and must fully commit to the breakaway competition.
Twelve elite clubs announced on Sunday their plans to launch a tournament to rival the Champions League in which they would be assured of qualification.
Real Madrid, Barcelona and Manchester United, among others, would compete in the Super League every season without risk of demotion.
The news has prompted a strong reaction throughout the football world, with governing bodies, rivals clubs, players, coaches and fans critical of the idea and its anti-competitive format.
An initial FIFA statement on Sunday read: "FIFA can only express its disapproval to a 'closed European breakaway league' outside of the international football structures."
Infantino, FIFA president since 2016, had not subsequently discussed the Super League in public until Tuesday's UEFA Congress, however.
But he made clear in Montreux, Switzerland, that the clubs involved could not continue in their domestic leagues, as proposed, while bans from international football for players at those clubs have been threatened.
"At FIFA, we can only strongly disapprove the creation of the 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," Infantino said.
"There is a lot to throw away for maybe a short-term financial gain of some. People need to think very carefully. They need to reflect and they need to assume responsibility.
"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 are in or you are out. You cannot be half in or half out."