Substitute Alexandre Lacazette pulled one back for the visitors but Gabriel Jesus wrapped up City's club record-extending 15th successive win after 74 minutes.
Arsenal may have had grievances over two of City's goals but the hosts were full value for their victory, which was also their ninth in succession in the Premier League.
The Gunners were actually confident and composed but their deployment of Francis Coquelin in the centre of a back five – a rare start for the Frenchman – indicated an uneasiness with City's attack.
Their concerns were justified, with City rapid and dangerous on the counter-attack. Aguero, who entered the field to a guard of a honour in recognition of becoming the club's record goalscorer in midweek, went close after two minutes.
The chance came after Raheem Sterling broke from deep and De Bruyne found Aguero but the Argentinian blasted narrowly wide.
Aguero also played in Leroy Sane but Sterling was unable to turn in his cross.
The opener came with 19 minutes gone after Petr Cech pushed away a snap-shot from De Bruyne. Sane retrieved the loose ball and De Bruyne played a one-two with Fernandinho before driving in a low shot from distance.
David Silva was the next to get behind the Arsenal defence but his pull-back evaded everybody before Sterling was wasteful from another good opening. Cech also had to react quickly when Laurent Koscielny turned a Kyle Walker cross towards his own goal.
Arsenal, who had been limited to long-range half-chances, finally threatened in the closing minute of the first half but Ederson beat away an effort from Aaron Ramsey.
City finally earned greater reward for their superiority early in the second half, although Arsenal complained after Sterling was adjudged to have been bundled over by Nacho Monreal. Aguero clipped in the spot-kick off the post.
The contest was not over, however. Arsenal started to show some teeth and had the ball in the net after Ederson spilled the ball and was pushed over the line by Ramsey. A foul was given but it was a warning the Londoners did not intend to roll over.
Ramsey forced Ederson to save again and Arsenal sent on record signing Lacazette. It proved an inspired move as the Frenchman reduced the deficit by lashing home a low shot following good work by Alex Iwobi and Ramsey.
City upped their tempo in response. Jesus, sent on for Aguero, was denied by Cech at point-blank range and the Arsenal goalkeeper also saved from De Bruyne.
The pressure paid off as De Bruyne slipped in Silva and his pull-back was turned home by Jesus. Again Arsenal took issue, believing Silva was offside, and Granit Xhaka showed frustration with the fourth official when substituted soon after, but City were not to be denied.