Yet it was an injury-enforced substitution to a key defensive player that freed up the champions and put them just three wins away from retaining their title.
Fernandinho went off with a knock after another important block, allowing Bernardo Silva to find space to create the opening goal before substitute Leroy Sane put the game beyond doubt.
United issue a response
Thunder storms on the horizon, tension surrounding Old Trafford. With both sides desperate for a win, there was a chess-like opening to the contest, underpinned by a couple of loose touches by Raheem Sterling. It was an issue that started to spread for the men in blue. Sloppy.
United, reverting to 5-3-2, had a gameplan. Press Vincent Kompany at the back, force a mistake and release the pace of Marcus Rashford. Ten minutes in, the City veteran was cautioned for blocking off his speedy opponent. Tightrope.
It was enough to formulate the first pulse of energy around the Theatre of Dreams. Paul Pogba let rip from range. Comfortable for Ederson.
The hosts had responded to the criticism burdened from the defeat at the weekend. Even Fred showed the confidence to cut across the ball from distance. Ederson was sprawling. Seconds later, Pogba picked out Jesse Lingard who diverted a volley wide on the stretch. Vintage from the former.
The game was threatening to open up and it did on 18 minutes. The Silvas combined, Bernardo stinging the palms of David De Gea from his namesake's lay-off. United countered immediately with Rashford only thwarted by the on-rushing Ederson. The pace was problematic.
Whilst Sterling and Sergio Aguero were on the periphery, Rashford was standing up and being counted for his club. A dipping effort from range flew just over. Technique.
The game settled. City regrouped but still lacked intensity. They finally created an opening with two minutes left of the half.
David Silva the architect, City finally started knitting passes in tight spaces. Sterling's fleet footwork created the smallest of gaps but he couldn't quite squeeze his effort past De Gea. Moments later, Aguero fired wide. Threat growing. Could it be built upon in the second half?
Bernardo breaks the deadlock, Aguero hits the post
For all of their attacking potential, Fernandinho is a key cog in the City wheel. After another emphatic defensive display, he hobbled off following an important challenge on Pogba just five minutes into the second half. An attacking replacement. Leroy Sane.
Ilkay Gundogan dropped into the anchor role and he started to pull the strings. United were almost unlocked when Sane's cross was hacked away by Victor Lindelof but eventually they found the breakthrough, the German again at the heart of the play.
Gundogan prowled patiently on the ball before finding the run of Bernardo, now with a free role more centrally. The Brazilian cut inside, used Luke Shaw as a shield and fired into the bottom corner, beating De Gea at his near post. 1-0.
City had their tails up and were inches from grabbing a second just moments later. A typically fast-paced City move was worked to Aguero who fired past De Gea but off the outside of the post.
Sane blasts through De Gea for number two
But United had a chance of their own within minutes. Kyle Walker stood and watched his hacked clearance before Rashford guided the ball across the box. Lingard had space to slot home but took his eye off the ball just before it arrived in front of his feet. Fresh air.
As United looked to respond, City were always a threat on the counter. Fred gave the ball away and Sterling broke forward. He released his fellow wide player and Sane let rip, firing straight through De Gea. Another mistake. Another goal. Game over?
Romelu Lukaku was introduced, the Belgian meeting chances either side of the 75-minute mark. The first, palmed away by Ederson. The second, scuffed wide. The far too common inconsistencies of the 25-year old.
United threw on Alexis Sanchez and Anthony Martial but City were in control. There was no response.
The full-time whistle signalled a seventh United defeat in nine games for the first time in over 50 years. Meanwhile, their noisy neighbours march on. Three wins from the title.
Takeaways from the game
Fernandinho injury works in City's favour
When the Brazilian limped off with just 50 minutes on the clock, you had to wonder if it was a sign that City's title hopes were drifting away. Yet the decision to introduce Leroy Sane prompted two tactical adjustments that opened a static City up.
Gundogan dropped deeper and was able to impact play after a quiet first half, whilst Bernardo was given more of a free role in a central position. United's midfield three were unable to pick up the runs, leading to the all important breakthrough.
Being a goalkeeper is a lonely place
One of the greatest number ones in the modern era, David De Gea's performances prior to this contest were under the microscope after a series of uncharacteristic mistakes. And there were two more here as his confidence continues to wilt.
The Spaniard shouldn't have been beaten at his near post for the opener before Sane's low strike went straight through a goalkeeper who is usually so good with his feet.