Football | Barclays Premier League
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United looked to have squandered a chance to claim the Manchester derby bragging rights when Pablo Zabaleta's equaliser with four minutes remaining completed a brave comeback from City, who had been given a lifeline by Yaya Toure's second half goal after trailing to a first half brace from Wayne Rooney.
But Alex Ferguson's side underlined their determination to wrestle the title back from City with a sensational response through van Persie, whose deflected free-kick handed the champions their first Premier League defeat of the season and their first home league loss since Everton won at Eastlands in December 2010.
"Today was a special one simply because they haven't lost at home for two years, both of us are contending at the top of the league," said Ferguson, who was angry that Ashley Young had a goal ruled out before City pulled one back.
"I thought we should have finished the game off. It should have been 3-0, the goal was perfectly onside, then they go up and score.
"Football can kick you in the teeth that way. They came back, were fighting like hell. But up to that point I thought we were far better than them.
"I think we can be proud of the fact that, opposed to last year when we gave them far too much respect, the players were determined to win it."
City manager Roberto Mancini added: "We didn't deserve to lose this game. We played very well.
"For 20 minutes they didn't touch the ball and the first chance they got they scored a goal.
"We recovered very well and we dominated the second half. We have showed we are a really strong team and we can win this title again."
United only had three attempts on target in the entire match, but they made them all count, starting in the 16th minute.
Young picked out Rooney and the United striker scuffed a low shot past wrong-footed City goalkeeper Joe Hart into the corner of the net.
City were rocked by that setback and Rooney netted again in the 29th minute, this time meeting Rafael da Silva's cross with a fine, first-time finish that gave Hart no chance.
That made Rooney the youngest player to reach 150 Premier League goals at 27 years and 46 days.
Young then had his goal harshly ruled out for offside in the second half when he fired home after van Persie's shot hit the bar.
Then Ivorian midfielder Toure slotted home from Carlos Tevez's pass in the 60th minute and City thought they had escaped when Argentine defender Zabaleta smashed in a low shot after United failed to clear a corner.
But there was a sting in the tale as United won a free-kick deep into stoppage-time and van Persie curled in a shot that deflected off Samir Nasri and flashed past Hart.
The remarkable finale was marred however when United defender Rio Ferdinand was hit by a coin thrown from the crowd as he celebrated the winner, while Hart had to stop another supporter who ran onto the pitch to try to reach Ferdinand.
Elsewhere, Nikica Jelavic and Steven Pienaar grabbed late goals to complete a remarkable fightback as Everton beat Tottenham 2-1 at Goodison Park to go fourth in the table.
Clint Dempsey struck for Tottenham in the 76th minute with the help of a deflection off Everton defender Sylvain Distin.
But David Moyes' men snatched a deserved victory thanks to an equaliser from South Africa midfielder Pienaar in the 90th minute and Croatia striker Jelavic's winner in the second minute of stoppage-time.
In the day's late game, Liverpool came from behind to win 3-2 against West Ham at Upton Park.
Former West Ham defender Glen Johnson fired the Reds into the lead with a brilliant strike into the top corner in the 11th minute.
Mark Noble equalised with a 36th minute penalty after referee Lee Probert ruled that Liverpool midfielder Joe Allen had handled Guy Demel's shot.
Steven Gerrard's own goal, a header from Matt Jarvis's cross, put West Ham in front in the 43rd minute.
But Liverpool substitute Joe Cole levelled against his old club before Hammers defender James Collins turned Jordan Henderson's cross into his own net under pressure from Jonjo Shelvey three minutes later.