Scholes, who signed a new one-year contract with the champions on Friday, headed home Patrice Evra's cross in the dying seconds to light up a tentative affair between the city rivals.
The win brought renewed optimism to second-placed United and with three games remaining puts them just a point behind league leaders Chelsea, who lost 2-1 to Tottenham Hotspur in the day's late match.
"I couldn't see a goal coming to be honest with you," United manager Sir Alex Ferguson told Sky television. "It (winning the title) would have been very, very difficult (without Scholes's goal).
"We are hoping Tottenham win tonight and if they do, the title is back on. Obviously it is a big boost to Tottenham because they can go fourth tonight."
City's defeat dented their hopes of securing the fourth and final Champions League qualifying spot. Spurs, one point behind in fifth place, will overtake them if they beat Chelsea at White Hart Lane.
"We hope Tottenham don't win but I think the crucial game will be when we meet Tottenham here (on May 5)," said City manager Roberto Mancini.
United, who included England striker Wayne Rooney in their team after an ankle injury, had the better of a frustrating derby where they enjoyed plenty of possession but lacked penetration.
City's apparent first half reluctance to go forward drew cries of 'attack' from the home fans but the closest they came to a breakthrough was a Carlos Tevez free kick held by keeper Edwin van der Sar.
The best chances before the break fell to the visitors. First, Antonio Valencia's header found Rooney with space and time but the striker, who has scored 34 goals this season, dragged his shot wide when he should have done better.
Valencia was again involved when his neat control and pass left Ryan Giggs with a toe poke from three metres but his tame effort failed to trouble Shay Given in City's goal.
DEJA VU
The hosts improved after the restart with Welshman Craig Bellamy screwing a shot into the side netting and City also failed to capitalise on a frantic goalmouth scramble.
The talismen of both teams were quiet at a sun-drenched Eastlands.
City favourite Tevez wilted against his former employers after a bright first half while Rooney went off with 20 minutes remaining after failing to leave his mark.
England manager Fabio Capello would have been relieved to see the burly forward emerge unscathed from another match ahead of the World Cup but the 24-year-old looked far from his usual bulldozing self.
With time ticking away and both sets of fans grumbling as they headed towards the exits, Scholes came to Ferguson's rescue and was mobbed by relieved team mates.
"He was absolutely fantastic. He is such a skilful player. He was wonderful today," said Ferguson.
The result brought unwanted deja vu to City fans who watched Michael Owen score an injury-time winner in United's 4-3 league victory at Old Trafford
