FIFA president Sepp Blatter has condemned the Premier League's proposal to play matches overseas as 'unacceptable' and an 'abuse of football'.
The Premier League clubs have agreed in principle to look at each playing an extra match every January in a foreign city.
Blatter though has vowed to do all he can to block the League's plans and warned that if they push ahead with the proposals it could torpedo England's bid for the 2018 World Cup.
The FIFA president's criticism follows strong opposition from UEFA counterpart Michel Platini and Asian federation chief Mohamed bin Hammam, and there is now a major doubt about whether the Premier League would even be able to find countries willing to hold the matches.
Blatter said: 'To try to have additional exposure and revenue by expanding the league around the world, I think this is not acceptable.
'It will not be acceptable to the FIFA executive committee, I am sure. This will never happen - at least this will not happen as long as I am the president of FIFA.
'We have not been contacted before by the League to ask us what we think of this idea. You speak about rude but I think it is an anti-responsibility.
'If you are the most prosperous league in the world and if you accept that everyone in football has a responsibility to maintain it not only as a business, but as a game.
'Then, all of a sudden you come out with a project which only has business and money behind it.'
Blatter said FIFA's statutes were clear that the matches would need the permission of the national associations of the countries where they would be staged - and that he would do all he could to block any attempt to grant that permission.
He added: 'According to the statutes and regulations, it is said very clearly that if you want to play any match in a foreign territory outside the country where the teams are coming from you need the authorisation of that association.
'I will bring it to the attention of the executive committee but you can be sure that the executive committee will reject such an inapplication of the statutes.
'And I will ask the national associations in a decision taken by the executive committee not to accept such an initiative which is definitely an abuse of the game. This is definitely abuse of association football.'
Blatter said he will take the controversy to FIFA's Congress if the Premier League insist on pushing ahead with their plans.
What will really worry the Football Association however Blatter's warning that the plans could affect England's bid for the 2018 World Cup.
Blatter added: 'If you go against the authority of FIFA and the decision-making body which is the executive committee then you cannot expect them to be in your favour later on.
'England will not be the only World Cup bid. I cannot imagine that when you go against the deciding body for the decision on the World Cup in an initiative that will not be accepted by this body, that you will enhance your chances. It will not be diplomatic.'
Blatter said he would give Premier League chief executive Richard Scudamore the opportunity to state his case to FIFA but would state his views 'perhaps even stronger'.
He added: 'Football cannot be like the Harlem globetrotters or a circus. You must keep the national identity of the clubs.'
A Premier League spokesman said: 'We look forward to the opportunity to meet with FIFA in order to discuss this matter in full.
'This was always the starting point in relation to this issue of sanction of our proposed international round and as such we will be making no further comment until after that time.'
Chelsea boss Avram Grant insists Blatter is wrong to say no to the Premier League proposal.
He said: 'I understand Mr Blatter but to say no to this idea it is not the right thing. We need to check many things but to play abroad you need to make the fixtures right. If everything is right I don't see any negative things about this.
'We can keep the tradition of the English League even if we play one game of the season away.
'The basis of football is not money. It is the only profession in the world that you are interested in because you have a lot of passion.
'I have had a lot of passion for this game since I was a child. You cannot separate this from the economic side.
'If it is only a matter of money, I am against it.
'There are many supporters of the Premier League abroad that maybe deserve one time of the year to see it live, then I don't think it is a bad idea. We need to be open and I cannot say 100% that it is a good idea, but we need to think about it.'
• Meanwhile, The Football Supporters' Federation have welcomed Blatter's opposition towards plans to hold Premier League matches overseas - but fear the proposal may still get the go-ahead.
The FSF launched a campaign called 'NO TO GAM£ 39' in the wake of last week's announcement that an 'international round' of top-flight matches was in the pipeline.
FIFA president Blatter last night delivered the biggest blow yet to the Premier League's proposals by revealing his determination to block them.
An FSF statement read: 'While Blatter's statement is welcome, this doesn't mean the danger of the Premier League pressing ahead has passed. Supporters need to keep the pressure up.
'We confirm that we'll be proceeding with next week's campaign meetings around England.'
FSF chairman Malcolm Clarke added: 'We might have gone one up 10 minutes into the game, but there's still a long way to go. We'll be fighting right to the final whistle.
'We can't afford to be complacent or think this proposal is off the table.'