The Dutchman’s deflected free-kick extends United’s lead over City at the top of the Premier League to six points and came after the home side had appeared to have fought back to secure a point. Wayne Rooney scored twice to give United a deserved 2-0 half-time lead, but a greatly improved second-half performance from City saw them pull one back through Yaya Toure before Pablo Zabaleta struck an equalizer with less than five minutes remaining.
The late intervention from Van Persie ends City’s unbeaten Premier League record and could have a massive impact on a title race that last season was settled on just goal difference.
The frenetic climax was in stark contrast to a rather cagey beginning. Despite the array of attacking talent in their side, it was very much a defensive first approach from United as Rooney, Ashley Young and Antonio Valencia dropped back into a midfield five.
City were in command in the early stages, dominating possession, although they showed little threat, other than a wild effort from Mario Balotelli.
In the 16th minute, United struck with a classic sucker punch. Young raced forward from his own half before knocking it onto Rooney who took the ball onto his right foot and then dragged a shot back across goal that went through two defenders and wrong footed an unmoved Hart low into the corner.
The goal, which at the time came out of nowhere, would prove the turning point in the period. As if going behind had not been enough of a blow for the home side they soon last their influential skipper Vicnent Kompany to injury. United suddenly assumed control.
While City still enjoyed ample possession there was a lack of width and cohesion going forward as everything was pushed through the middle. It was likely to take a piece of individual skill to get the breakthrough and Aguero almost provided it as he wriggled through a succession of United challenges on the edge of the box, but eventually shot tamely at David de Gea.
United, repeatedly breaking with pace, width and intent, put themselves in a commanding 2-0 lead just before the half-hour mark as Rooney found the same bottom corner of the net.
This time Valencia set up Rafael down the right and the Brazilian picked out Rooney with a good low cross and with the midfield not tracking back and the Kolo Toure unable to get out fast enough, the England forward had time to side foot the ball past Hart’s despairing dive.
Gareth Barry missed a half-chance from the edge of the box at the end the first half, but City came out with gradually increased urgency following the restart.
On one of the first occasions where City increased the pace, Gael Clichy found Aguero on the edge of the box and the Argentinean curled just wide.
Just prior to the hour mark, the game exploded. Van Persie so nearly put the result surely beyond doubt as he curled a wonderful effort from 18 yards with his weaker right foot that hit the post before Young slotted home. The goal was ruled out for offside, although replays showed the he was at worst level with the last defender.
So nearly out of the game, City made the most of their reprieve and almost immediately made it 2-1. De Gea will have been left crestfallen at having made two spectacular saves, first from substitute Carlos Tevez and then from Silva, before the ball was played back to Toure who managed to evade the goalkeeper’s fingertips and find the bottom corner.
United were soon left ruing the officiating for the second time in the contest as Patrice Evra was bundled down by Kolo Toure going across his body, but referee Martin Atkinson was unmoved.
As the final 15 minutes arrived the match kicked up a gear once more. At one end, Van Persie could have sealed the points but was unable to control his header. Then streaming forward Silva tuned inside Evra in the box but his shot from close range struck the shoulder of De Gea before bouncing up off the cross bar.
City would not be denied much longer. With just four minutes remaining a corner broke to Zabaleta on the edge of the box and the trusty full back crashed a low shot into the corner of the net through a host of bodies to send the Etihad into raptures.
The momentum looked to be with City for the final stages but one again United showed that their attacking talent means they can never be counted out.
In his first Manchester derby, Van Persie made himself a hero as he curled a free-kick from 25 yards that took a vital deflection off the outstretched leg of Nasri to take the ball past Hart and into the corner.
The final stages were sadly marred by discontent both on and off the pitch. Rio Ferdinand was left bloodied by a coin thrown onto the pitch and Tevez was lucky to avoid a sending off for aiming a kick at Michael Carrick.
But the greatest damage had arguably been done to City’s chances of retaining their title, as United took a commanding advantage.