Pep Guardiola's side made it eight consecutive wins in all competitions and dominated for long periods against Chelsea, despite their preparations for the match being disrupted by Sergio Aguero suffering a broken rib in a car accident.
The hosts showed limited attacking intent, which was further compromised by top scorer Alvaro Morata limping off in the 35th minute due to an apparent left hamstring injury.
An exemplary showing from the home defence, in which Andreas Christensen was outstanding, meant City struggled for a regular flow of clear-cut chances despite their superiority.
That was until De Bruyne seized the moment, something his game-breaking goal against Shakhtar Donetsk in midweek demonstrated he is increasingly adept at doing.
The Belgium midfielder collected a return pass from Gabriel Jesus in the 67th minute before unleashing an unerring left-footed finish from outside the area.
The result places City ahead of Manchester United at the summit on goal difference, although their advantage in that regard was slashed to one by Jose Mourinho's men thumping lowly Crystal Palace earlier on Saturday.
Chelsea are fourth, six points off the pace heading into the October international break.
Conte preferred Cesar Azpilicueta to the more attack-minded Victor Moses at right-wing back but the Spain defender was involved when Chelsea crafted the game's first opening in the third minute.
Azpilicueta played in N'Golo Kante down the right channel and the midfielder's clipped cross was glanced over by Morata.
Chelsea goalkeeper Thibaut Courtois restarted with a short goalkick in the 12th minute and dallied after receiving possession back. He was fortunate to see a clearance thud into City striker Jesus and go over the crossbar.
City were dominating possession but needed a brave headed clearance from Nicolas Otamendi in the 26th minute as Antonio Rudiger's cross threatened the near post, and Ederson scrambled to deny Azpilicueta on the follow-up.
The visitors sprung up the other end in slick fashion, only for Raheem Sterling to float a cross too far in front of Jesus and David Silva, who were queuing up to finish.
Silva took matters into his own hands as Courtois thwarted a stinging drive at his near post, before the Spain playmaker saw one of his compatriots in the opposition line-up depart early.
Willian's introduction in place of Morata meant Chelsea were operating without a recognised striker and City continued to make most of the running in attacking terms - Courtois reacting magnificently to keep out Fernandinho's 44th-minute header.
Guardiola's men continued to zip precise passes around after the restart, with the Chelsea defence increasingly well-manned.
Sterling hooked a left-footed volley over in the 54th minute – a rare instance of an attacker finding space inside the home penalty area.
City's defence switched off and were bailed out by Ederson after the hour passed, the Brazilian denying Eden Hazard on the end of Cesc Fabregas' cleverly disguised free-kick.
Silva's decision to take a touch on the end of Sterling's 66th-minute cutback proved his undoing before Jesus nicked another ball from the England winger out of his path.
It fell to De Bruyne to give his fellow playmaker a lesson in how to be clinical when he lashed beyond countryman Courtois.
Conte sent on Michy Batshuayi and Pedro in place of Hazard and Tiemoue Bakayoko to chase an equaliser but it was City who almost embellished a stirring victory when Rudiger headed Jesus' volley off the line in the 85th minute.
Key Opta stats:
- Chelsea have dropped eight points in four Premier League home games so far in 2017-18; two more than in the whole of 2016-17 (6).
- Manchester City have kept four consecutive clean sheets in the Premier League for the first time since September 2015 (six games in that run).
- Chelsea have failed to score in consecutive home league games for the first time since November 2012.
- Chelsea posted a 38% possession figure in this game, their second-lowest in a home Premier League game since 2003/04 (29.6% v Man Utd in April 2015).
- Pep Guardiola enjoyed his first-ever victory against Chelsea in eight games in all competitions (not including shoot-out wins), after previously losing three and drawing four.
- Kevin De Bruyne has been directly involved in 15 goals in his last 17 Premier League appearances (3 goals, 12 assists).
- Nine of De Bruyne’s last 11 goals for Manchester City in all competitions have come from outside the box, including each of the last four.
- Gabriel Jesus has had a hand in 16 goals in his 16 Premier League games, scoring 11 and assisting five.