A tightly contested game at Etihad Stadium came to life 20 minutes from time as De Bruyne intervened decisively.
Chelsea did not see much of the ball but had its chances to get on the scoresheet too, with Romelu Lukaku and Hakim Ziyech particularly wasteful on the counter-attack.
Pep Guardiola's City has now won 12 league games on the bounce, and it is difficult to see how it can be denied making it back-to-back titles come May.
City dominated much of the first half but was grateful for poor decision-making and execution from Lukaku and Ziyech on two occasions as Chelsea looked to counter early on.
The best chance for the hosts in the opening 45 minutes came when an effective high press set Jack Grealish through on goal, but Kepa Arrizabalaga deflected the former Aston Villa man's shot behind with his left leg.
The visitors should have taken the lead two minutes into the second half when Lukaku was sent clear by Mateo Kovacic, but Ederson palmed his shot away before Ziyech lifted the rebound over the bar.
The league leaders finally broke the deadlock in the 70th minute when former Chelsea man De Bruyne cut in from the left side before expertly firing past the despairing dive of Arrizabalaga from 22 yards.
The Blues tried to find an equaliser, but City showed its solid side to clinch the three points, moving a significant step closer to lifting the Premier League trophy once more.