United had put up a decent fight in the first half, going in 2-1 down at the break, but City’s quality showed after the interval with Ralf Rangnick’s side looking increasingly demoralised.
City have 69 points from 28 games with Liverpool on 63 from one game less. United slip down to fifth place, a point behind Arsenal who beat Watford on Sunday and have three games in hand.
Belgian De Bruyne was outstanding, running the game from central midfield and then presenting himself as a threat in the box.
United were without Cristiano Ronaldo and Edinson Cavani through injuries and surprisingly Rangnick opted to play Paul Pogba and Bruno Fernandes in forward positions.
City made the perfect start with De Bruyne putting them ahead in the fifth minute, slotting home a low pulled-back pass from Bernardo Silva after they overloaded the left side.
But United drew level through a superb curling shot from Jadon Sancho, who took his time and cut inside after a swift break before beating Ederson with his confident strike.
But Belgian De Bruyne restored City’s advantage finding the target after Phil Foden had powered into the area and seen his shot parried out by David De Gea.
|Manchester City’s Kevin De Bruyne celebrates scoring their second goal with Phil Foden. Photo: Reuters
City dominated after the break and made it 3-1 when De Bruyne struck a corner deep to the edge of the box and Mahrez met it with a first-time drive which took a slight deflection off Harry Maguire.
Mahrez completed the victory with a goal that was initially flagged as offside but VAR found Alex Telles had played the Algerian onside before he latched on to an Ilkay Gundogan pass and blasted in off the shoulder of De Gea.
The scoreline was a fair reflection of City’s dominance and manager Pep Guardiola was full of praise for his team.
“It was excellent from the first minute. We played really well and had to be patient in the first step,” said the Spaniard.
“Football is emotions. It’s tactics, definitely, but it’s also emotions. Without the ball, we are a team with desire and passion to regain the ball from the first minute to the 90th,” he added.
Rangnick felt his tactics had been the right way to take on City before the gulf in class became evident.
“It was working. For us it was clear if we want a chance to win the game we have to do a lot of running. You have to be in attacking and hunting mode and we did that in the first half. The third goal killed us off in the end,” he said.
“It’s difficult, if we attack them very high there is a lot of negative running you need to do. The third goal is a brilliantly taken corner and it is almost impossible to defend that. The second half they were the better team and they showed the quality they have. We struggled especially after they scored the third one.”