McEnroe, a four-time US Open champion and three-times Wimbledon winner, is not ruling Federer out of contention for the latter stages of the tournament but he feels it may now be too much to expect the Swiss to go all the way.
"To me, it's obviously going to be a lot more difficult at this stage," McEnroe, now a television commentator with ESPN, said on a conference call.
"I don't see at this stage him being able to go through all seven (rounds) and have to beat at least two of these (top) three guys.
"Maybe he would use that type of thing as incentive. When you've won 17, you clearly think you can win another one. To me, there comes a point, even as great as Roger has been for so many years, that it catches up to you a little bit," McEnroe added.
Beaten by the 116th-ranked Sergiy Stakhovsky in the second round at Wimbledon, Federer also lost to Federico Delbonis in the Hamburg semi-finals and 55th-ranked Daniel Brands on home soil in Gstaad.
He fared a little better in Cincinnati last week, reaching the quarter-finals where he was beaten by eventual winner, and US Open favourite, Rafa Nadal.
McEnroe believes that while Federer's experience and ability mean he will still be a factor, grand slam win number 18 may be a step too far now.
"There are certainly scenarios where he could easily still get late into an event and even to a final," McEnroe said. "Andre (Agassi) got to the final of the Open at 35, so there's no reason to believe he couldn't do it.
"At Wimbledon I could see him going late into an event, a final. I could see it on a hard court...but I personally think that at this stage it's going to be quite, quite difficult for him to win another one."
With Nadal, Novak Djokovic and Andy Murray all displaying better form and consistency, McEnroe expects tough decisions ahead for Federer, especially if he remains well behind those three in the rankings.
"These guys are hungry," said McEnroe. "There's other guys that want get on the board. He's 32. He's going to have to at some stage decide how bad he wants it if he does dip lower in the world.
"I doubt he'll enjoy being in that spot. All these factors are going to start to come into it. Now, he can shut everyone up if he was able to go all the way at the Open and he could still keep himself in the running."
McEnroe also felt that Federer has lost some of his sharpness and balance.
"I think one of the things you notice a little bit is possibly he's slowed down a little bit," the American said. "The balance and the movement are not quite as (Rudolf) Nureyev-like as they were in the past.
"So he's reaching for more balls and therefore miss-hitting more shots. It doesn't seem like he's been able or willing to make that adjustment where he's got to either play safer or take that extra step to balls."
For McEnroe, Federer no longer seemed to have the same self-belief in his movement about the court.
"That first quick step you got to take to take advantage of a ball, especially how hard as they guys hit it," he said.
"He's so used to being able to go big and hit pretty much everything he wants. And part of why he's so great is because he's stubborn and he believes in himself, so he's unwilling to change a whole lot."
