The Red Devils find themselves in the strange position of being behind their local rivals heading into the first all-Manchester showdown of the Barclays Premier League season.
And Ferguson is acutely aware that if the unbeaten Blues manage to register only their second Old Trafford success in 37 years, it will put them five points clear of United, a position from which it would be by no means certain the champions could recover.
However, whilst Ferguson is not actively embracing thoughts of defeat, he does know from past experience how his squad comes good over the final few months, when the battle for honours on all fronts is intensifying.
“This game could be significant at the end of the season,” said the United boss.
“It is a six-pointer. It will make a difference to whichever team wins it.
“But it is early doors and you can recover. There is no doubt about that.
“With our record in the second half of the season, you hope that we will be better.”
City are the latest rival for a team who has been at the top of the league for two decades.
In their various guises, Liverpool, Arsenal and Chelsea have all been disposed of. Now Ferguson has to deal with City.
It is a battle he is relishing.
“We always accept a challenge at this club,” he said.
“We have had that time and time again. This is another situation.
“It is another game in the history of our club and we have to do something about it.
“You don’t always want to be behind clubs, like we were for a couple of years with Chelsea.
“But we showed we had the vigour and determination, and also the decision-making that got us back in front of that particular football club.”
The same quest now stands in front of United, even if City’s current lofty status is not quite so well advanced as Chelsea, who won two titles before Ferguson and his players could react.
Ferguson now has first-choice central defenders Nemanja Vidic and Rio Ferdinand available for the first time since the opening day of the season.
However, the memory of United’s second-half display in the Community Shield a week before must be playing on Ferguson’s mind.
Although the Red Devils were the better team, they were two goals behind at the break.
It took the half-time introduction of Jonny Evans, Phil Jones and Tom Cleverley, who is set to resume training on Monday after injuring his foot at Bolton seven weeks ago, to transform the contest in United’s favour.
That was probably one of the reasons why Ferguson had no desire to offer any opinion on the myriad of options at Roberto Mancini’s disposal.
“He has his job to do like everyone else,” said the United boss.
“We have all got difficult jobs picking teams. Mine is exactly the same. I am pondering a couple of positions myself.”
Since then, City have dropped just two points, when they surrendered a two-goal lead at Fulham, and Ferguson accepts the Blues are in fine form.
“It is an exciting prospect,” he said.
“City have done fantastically well and if they had not thrown a two-goal lead away at Fulham they would have been top of the league with a 100 per cent record.”
Given their respective records this term, a memorable tussle is in prospect.
However, although the last few years have brought a seven-goal thriller settled by Michael Owen in stoppage time, Wayne Rooney’s last-gasp goal to seal a Carling Cup semi-final triumph and Yaya Toure’s FA Cup semi-final matchwinner, in addition to Rooney’s spectacular overhead kick in the corresponding fixture last term, Ferguson is not certain another sensational contest is on the horizon.
“There could be goals – but it could also be disappointing,” accepted Ferguson.
“It is a major game. It is very seldom in major games that you get a lot of goals.”