Even before the game fans suspected the Gunners had a mountain to climb when Arsene Wenger dropped Lacazette and started Francis Coquelin and Alex Iwobi.
Unsurprisingly, both players had a shocker at the Etihad, with Arsenal's best period of the game only coming when changes were made.
Kevin De Bruyne opened the scoring in the 19th minute with a lovely left-footed drive before Sergio Aguero made it 2-0 from the penalty spot just after the break.
Lacazette then brought Arsenal back into the contest within nine minutes of coming on, but in the 74th minute, City killed the game off in controversial circumstances.
David Silva was in a clear offside position when he was played through, but the linesman didn't flag, allowing the Spaniard to pick out Gabriel Jesus for City's third of the game.
Arsenal's players certainly didn't help themselves by just standing still, assuming the referee would blow for offside, but the wrong decision was made nonetheless.
In his post-match interview, a furious Arsene Wenger slammed the officials for allowing Jesus' goal to stand.
"You have seen what I've seen.The fact that you tell me it's an offside goal shows enough," said the Frenchman.
"I don't want to take anything away from their quality but it happened at a moment when we were in the game."
Arsenal were utterly outclassed at the Etihad, but it was in midfield where they really lost the battle.
The midfield partnership of Granit Xhaka and Coquelin was nowhere near good enough and the most worrying thing for Arsenal fans was how unbothered they looked about losing.
There was one embarrassing moment in the second half that epitomised just how poor Arsenal were in the middle, when Silva literally ran circles around them.
In the video below, at 3-1 down, Arsenal's players allow the Spaniard to dribble the ball in a full circle without applying any pressure.
SILVA MAKING IT LOOK EASY
Shocking. Not one Arsenal player tried to dispossess Silva as he ran past five of them and eventually passed to a teammate.
Football fans couldn't quite believe what they were seeing, as you can see in the Twitter reaction below.