The former Wimbledon champion has struggled all season to find his best form after undergoing back surgery last September.
Murray admits he has been far too up and down, mixing encouraging performances with bewildering ones, none more so than the quarter-final loss to Grigor Dimitrov that brought his Wimbledon title defence to an end.
Heading into the last grand slam of the year, which begins on Monday, Murray is still looking for his first final and first top-10 victory since winning Wimbledon.
McEnroe, who will return to London for the Statoil Masters at the Royal Albert Hall in December, said: "It's difficult to say what's happening with Andy.
"It seems like the physical issues are behind him - it's impossible to say for sure from the outside but that's how it looks.
"It's been a process for him to come back from those issues so that takes its toll on the confidence, and he made a big change - I thought he and Ivan (Lendl) worked well together.
"To change course when he did is tricky so it remains to be seen what happens there. You need to give it more time to judge, but you sort of feel like the US Open would be a time he needs to step up because it's been a struggle compared to what it's been the last couple of years."
The end of his hugely successful partnership with Lendl in March certainly did not help Murray's confidence levels.
The US Open will be Murray's second grand slam with Amelie Mauresmo in his corner, and McEnroe is reserving judgment on whether the partnership can be a success.
The American, who was himself briefly linked with the role, said: "Amelie Mauresmo's appointment was a little out of left-field and an unusual choice, but she's had some coaching experience and she's been out there herself so she can bring things to the table.
"You always need to give these things some time to see how they relate to each other and whether she can make that little difference. Can she help him find that extra two to five per cent? That's the key. It remains to be seen."
Murray has been helped by the withdrawal through injury of defending champion Rafael Nadal, which will elevate the 2012 winner from ninth to eighth seed.
That still means he could play either world number one Novak Djokovic or Roger Federer, who he lost to in Cincinnati last week, in the last eight.
Djokovic has struggled on the North American hard courts so far, losing early in both Toronto and Cincinnati, but McEnroe makes him the man to beat.
"I think Novak had an incredible run at Wimbledon and it seems to me he is waiting for the Open," said the four-time US Open champion.
"I don't think it matters a whole lot what's happened with his results in the summer. To me, he's still the favourite going in.
"There's a cast of other characters that will want to break through and to finally put their names in the record books, and the most obvious ones are Dimitrov and (Milos) Raonic, but Djokovic is still the favourite."
:: The Statoil Masters Tennis at the Royal Albert Hall takes place from 3-7 December. Tickets are available at www.Statoilmasterstennis.com.