The Blues fell behind to a Marcus Rashford goal on 16 minutes and couldn’t find a way back into a game that also saw Joe Hart stretchered off with a leg injury.
Now City must regroup and return from the international break focused on qualifying for next season’s Champions League as what has been a largely disappointing Premier League campaign continues.
The 171st Manchester derby may not have been the top-of-the-table clash it has been over the past five years or so, but, there was still plenty at stake, not to mention local bragging rights.
City started the brighter of the Manchester clans and Jesus Navas twice went close to giving the Blues an early lead, first when he volley a David Silva cross wide and then when he forced David De Gea into a save at his near post.
But it was United who struck first on 16 minutes when Marcus Rashford picked up the ball outside the City box, slipped it past Martin Demichelis and then placed a low shot past Joe Hart.
And it could have been worse three minutes later as Anthony Martial fired in a powerful shot from the edge of the box that Hart did well to beat out.
The Blues had been rocked and lost Raheem Sterling after 25 minutes - he was replaced by Fernando which in turn allowed Yaya Toure to push forward as part of the midfield trio behind Sergio Aguero.
As the half wore on, so the home support grew more frustrated at the lack of creativity and opportunities for the Blues who reached the break having not found the net in more than four hours of action.
The second period also started badly for the Blues as a poor Martin Demichelis back pass was chased down by Rashford and as Hart bravely slid the ball clear, he appeared to pull his calf muscle in the process.
It was a major for the Blues with the half barely a couple of minutes old and Willy Caballero replaced the England keeper who could now face several weeks on the side-lines.
Wilfried Bony replaced Demichelis moments later. In turn, Fernandinho moved into central defence as Manuel Pellegrini shuffled his pack in hope of changing the hosts’ fortunes.
City needed a spark of genius, a moment of brilliance or a slice of luck to get back into a game that seemed to be slipping away from them, no matter how hard they tried.
Yaya Toure’s burst down the right and clever cross very nearly resulted in an equaliser as Aguero’s header struck the outside of the post but United held firm.
The Blues continued to try and find a way back into the game and Bony came close on a couple of occasions, but the Reds continued to defend resolutely as they protected their slender but crucial advantage.
Aguero and Bony had further chances to at least rescue a point for the increasingly desperate Blues, but despite six minutes of added time, City’s goal drought stretched to a third successive game on an afternoon that the home fans will want to forget as quickly as possible.
