A remarkable derby even by Manchester standards ended with City celebrating one of the biggest wins in the fixture's history and the humiliated ten-man Reds nursing their wounded pride.
City's joyous six-hit surpassed even the 5-1 triumph of 1989 to leave Roberto Mancini's rampant team five points clear at the top of the Barclays Premier League on an extraordinary afternoon.
United had never conceded so many at home in the competition, and it was hard not to see this as a watershed moment in the wavering balance of power at the pinnacle of the English game.
Mario Balotelli's double seemed to stun the champions, who tumbled to their first home defeat in 18 months as Sergio Aguero ensured victory with his tenth goal in nine games for City before Edin Dzeko (two) and David Silva piled on the agony.
Jonny Evans' dismissal with City 1-0 ahead and the whole second half to be played did the home side no favours, but there could be no argument that Mancini's side fully deserved their win.
It was the first time in 20 home games that United had failed to win, but sometimes the stats do lie, and first-half figures would not have done justice to a battling City performance that both bemused and frustrated their hosts.
For while United enjoyed the bulk of the possession, it was City who overcame an admittedly tentative opening to make their presence felt and take the lead through Balotelli's strike.
Ashley Young threatened to do the Blues untold damage as the England winger initially tormented Richards, but as he got the measure of his opponent, so did City all across the pitch, and when Silva dazzled four opponents in the penalty area, the Blues' swagger returned.
Not enough to dominate the game yet, but certainly enough to wrench the opening goal from the tension of the game and put a gradually-acclimatising City in control, however flimsy their lead.
Silva, who pulled his weight with defensive tackles as well, showed that simple can be just as effective as magical with the straightforward pass that found Milner on the overlap.
Milner, so important in creating the midweek winner against Villarreal, responded with the perfect pull-back for the oncoming Balotelli to steer instantly into goal
The Italian's precision and the measured pace he put on the shot meant De Gea had no chance of getting across to the ball before it squeezed inside his left-hand post by a matter of inches.
His celebration - he lifted his shirt to reveal a T-shirt emblazoned with the enigmatic legend "Why Always Me? - earned him the inevitable yellow card from referee Mark Clattenburg, as if he cared.
Richards even had a cheeky 40-yard lob go well wide in the buoyant climate that goal created, but before half-time both Anderson and Wayne Rooney had chaances they blasted straight at Joe Hart.
The key moment of the second half arrived barely a minute into the restart, as Jonny Evans pulled Balotelli back on the edge of the area as he chased Sergio Aguero's first-time pass.
Referee Clattenburg had no hesitation in showing the defender a red card, leaving United a man down as well as a goal down, and they might have been two down within a few minutes.
Anderson bundled into Richards inside the penalty area and the raiding defender could not help but go down. Television replays suggested that Mr Clattenburg should have pointed to the spot.
But City now had a grip on the game, and after 59 minutes the same combination for the first goal struck again to give the Blues a two-goal lead and send the travelling army wild.
Silva fed Milner and this time the England midfielder, having a great game, crossed low to the far post where Balo steamed in to convert the chance.
It left City in the same position they achieved at Wembley in the Community Shield, only to be pipped 3-2, but this time there was to be no miraculous recovery for the ragged Reds.
Aguero made sure of that by snapping up the third goal with 20 minutes left, Balotelli's backheel to Milner followed by Richards' incisive cross for Aguero to slide past the exposed De Gea.
Darren Fletcher pulled one back for United after 80 minutes, a brilliant strike from the edge of the box to give Hart no chance, but City were far from finished with annoying the neighbours.
First substitute Edin Dzeko bundled in a fourth goal with his knee after Joleon Lescott pulled the ball back for him with Gareth Barry's header from a corner going wide.
Then with Old Trafford emptying, Silva slipped a fifth through the goalkeeper's legs and, seconds before the whistle, the Spaniard's sublime cushioned volley of a pass allowed Dzeko to blast goal No.6.