Three weeks ago, United already had one hand on a record 20th title after City's defeat at Arsenal left Sir Alex Ferguson's team a hefty eight points clear with only six games remaining.
But a poor run of results from United, which has seen them take only four points from a possible nine, has suddenly given City the chance to put themselves back on pole position as the finish line looms into view.
City manager Roberto Mancini has insisted that he still expects United to win the league, citing the champions' experience in closing out title run-ins.
"I probably expect us to lose to Manchester United," Mancini said last week. "Their players are used to playing under pressure every year. But we don't have any pressure as we have no chance of winning."
Mancini's downbeat public utterances are unlikely to fool anyone: the Italian knows that his expensively-assembled side can return to the top of the table with a victory on Monday.
Wins at Newcastle and at home to Queens Park Rangers would then guarantee City the league crown, provided United are unable to make up their rivals' significant advantage in goal difference, which currently stands at plus six.
Arguably United's biggest asset in what promises to be a nerve-shredding occasion on Monday is their manager.
After 25 years at Old Trafford, little fazes Ferguson and the 70-year-old is relishing the challenge from opponents whose seemingly limitless wealth makes them the biggest threat to United's position at the summit of the English game.
Ferguson has calmly noted that the title is still United's to lose, and that a draw at Eastlands on Monday would leave his team in control. City, who must win, have no such margin for error.
"We know the exact situation we are in here," Ferguson said. "We are in a better position than Manchester City.
"We can get two results, they can only get one. They have to win. We can draw or we can win, although you know my attitude and the club's attitude. We will be trying to win."
United have already demonstrated that they have the know-how to get a result at a ground where City have dropped just two points all season, winning January's FA Cup third round tie 3-2.
Yet Ferguson must be concerned by the sudden frailty of a United defence that was punctured repeatedly by Everton last weekend in a 4-4 draw.
City, who humiliated United 6-1 at Old Trafford in October, have rattled in 12 goals in their past three games, and their nimble strikeforce of Sergio Aguero and Carlos Tevez will fancy their chances of adding to that haul if Rio Ferdinand and Jonny Evans have another off-day.
Of all the storylines to emerge from this year's Premier League page-turner, it is the re-emergence of Tevez that is potentially the most compelling.
Ostracised by Mancini after his infamous refusal to warm-up during the Champions League defeat at Bayern Munich in September, the former United striker then disappeared to Argentina for three months of unauthorised leave.
Mancini, who had previously said Tevez would never play for the club again, has been forced to reverse his stance during the run-in, particularly after ill-discipline saw Mario Balotelli sidelined for three games.
Tevez has responded to his recall by delivering goals, adding an injection of verve to a City forward line that had been struggling to reproduce their scintillating early season form.
Ferguson was cool about the possible impact of Tevez, who has scored three times in five previous games against United, on Monday's derby.
"We have not watched the games a lot, but he scored a hat-trick," Ferguson said. "That is an impact.
"We will just have to wait and see what he does on Monday."