De Bruyne scored twice and set up John Stones’ goal before Erling Haaland capped the demolition at the Etihad Stadium as City showed why they have been champions four times in the last five seasons.
Pep Guardiola’s side have trailed unexpected pace-setters Arsenal for much of the campaign, but the Gunners have choked over the last month while battle-hardened City show no signs of being affected by the pressure.
Second placed City are now just two points behind Arsenal with two games in hand.
City will become champions for a third successive season if they win six of their last seven matches.
Few would bet against them after a blistering run of seven consecutive league victories reeled in Arsenal.
Unbeaten in their last 16 games in all competitions, City have won 13 of their past 14 games as they chase a remarkable treble.
They booked an FA Cup final date with Manchester United last weekend and face Real Madrid in the Champions League semi-finals.
“The connection between Kevin and Erling is extraordinary, today we tried to use it as much as possible,” Guardiola said.
“I know the next three games are really important. The reality is today we are two points behind Arsenal, they are in front of us.”
While City eye a memorable end to the season, Arsenal, who were eight points clear at the start of April, have failed to win any of their last four league games.
Arsenal’s third defeat against City in 2023 could prove the final blow to their hopes of winning the title for the first time in 19 years.
Mikel Arteta’s young team have lost their nerve at the worst possible time, with three successive draws, featuring a pair of blown two-goal leads, followed by their first loss in 11 league games.
“The better team won. They were probably at their best in the first half and we weren’t at our level. In terms of the basics we didn’t do it,” Arteta said.
“There’s still five games to go. I’ve been in this country 22 years and things change a lot.”
De Bruyne started the demolition in the seventh minute when he took Haaland’s deft pass and surged towards the Arsenal area before smashing a low strike past Aaron Ramsdale from 20 yards.
Stones rewarded City’s incessant pressure on the stroke of half-time when he headed in De Bruyne’s free-kick, with the goal awarded by VAR after initially being disallowed for offside.
Imperious City were in complete control and De Bruyne put the result beyond doubt with another clinical finish from Haaland’s pass in the 54th minute.
Rob Holding smashed home in the 86th minute, but the defender’s goal was no consolation for reeling Arsenal.
With virtually the last kick of the game, Haaland slotted under Ramsdale for his 49th goal in all competitions this term and his 33rd in the league, beating Mohamed Salah’s record for a single 38-game Premier League season.
Elsewhere, Chelsea crashed to a fifth successive defeat under Frank Lampard as their west London neighbours Brentford won 2-0 at Stamford Bridge.
In his second spell as Chelsea boss after replacing the sacked Graham Potter until the end of the season, Lampard has failed to spark a revival from his troubled team, who were booed off at full-time.
With former Paris Saint Germain and Tottenham manager Mauricio Pochettino reportedly close to taking charge, Chelsea are enduring their worst run since 1993 after their winless streak extended to eight games.
Cesar Azpilicueta’s 37th minute own goal and Bryan Mbeumo’s 78th minute strike left 11th placed Chelsea in danger of finishing in the bottom half of the table for the first time since 1996.
“The fans feel down because they are used to success. We have to take it on the chin,” Lampard said.
Liverpool kept alive their slender hopes of a top four finish with a 2-1 win at West Ham.
The Hammers took a 12th minute lead through Lucas Paqueta’s spectacular strike, only for Cody Gakpo to equalise from long-range five minutes later.
Joel Matip’s 67th minute header moved sixth placed Liverpool within six points of fourth placed Manchester United, who have two games in hand.
Nottingham Forest climbed out of the relegation zone as they beat Brighton 3-1 at the City Ground to win for the first time in 12 games.
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