On Monday League Managers' Association chief executive Richard Bevan warned that the numerous foreign-based owners of England's top flight clubs wanted to guarantee membership of the elite league by scrapping relegation.
However, the Premier League's most successful manager slammed talk of a move that would effectively undermine the bedrock of English league football since it began in the 1880s.
"If you look at the Championship at the moment, we have eight teams with tradition and history," Ferguson was quotes in British media on Tuesday.
"What do you say to those eight teams? That they can never play in the premier division. I think that would be absolute suicide for the rest of the league and particularly the teams in the Championship.
"You might as well lock the doors. The only place you can make money and realise your ambitions is in the Premier League and you can't take that away from clubs like Nottingham Forest, Leeds United, Sheffield United and Sheffield Wednesday.
"All these great teams, who formed the nucleus of our old First Division all those years ago. It would be unwise."
American-owned United are one of 10 of the 20 Premier League in foreign hands, with league leaders Manchester City and 2010 League and FA Cup double winners Chelsea among the others. For any change to be made to the structure or laws of the Premier League, 14 of the 20 need to vote in favour.
Even if enough club owners joined forces to try and tear up the established system of relegation as a means of safeguarding their investments, the Football Association could still veto any major changes to the structure of football.
"The FA's share can be used so it has to approve any major rule change. This covers changes to promotion and relegation," an FA spokesman said on Tuesday.
The FA objected in 2008 when the Premier League discussed a plan to play a match abroad with a "39th game."
There is no relegation and promotion in the major U.S. sports of American Football, ice hockey, baseball and basketball, so the concept is alien to the American owners of United and Liverpool, Aston Villa or Sunderland.
Last week Liverpool's managing director Ian Ayre was widely criticised for suggesting that Liverpool, owned by American John W. Henry's New England Sports Ventures, could raise more overseas television revenue if it broke away from the collective marketing stance of the Premier League.
