Raheem Sterling scored a hat-trick with Gabriel Jesus and Sergio Aguero also on target as Hammers boss Manuel Pellegrini, who managed City between 2013 and 2016, made a losing start to the campaign.
City made a surprisingly slow start to the match and West Ham had penalty appeals waved away by referee Mike Dean in the eighth minute when Manuel Lanzini went down under new signing Rodris challenge.
At the other end, Lukasz Fabianski turned Bernardo Silvas fierce drive away for a corner before David Silva dragged his shot wide after being set up by Riyad Mahrez.
The Algerian then fired an effort of his own into the side-netting as the visitors began to move through the gears.
Pep Guardiolas team took the lead in the 25th minute when Kyle Walker easily beat Aaron Cresswell and fired in a cross that Jesus flicked past Fabianski.
The goal lifted last seasons Premier League champions and Silva and Mahrez went close to doubling their lead as City enjoyed a purple patch just before half-time.
Sterling scored his first goal six minutes into the second period after great play by Kevin De Bruyne, the Belgian cutting through the Hammers defence before playing in the former Liverpool star to slot the ball past Fabianski.
City thought they had scored a third goal two minutes later when Jesus finished off a sublime move but, after a lengthy delay, the goal was ruled out by VAR for offside.
Issa Diop headed Robert Snodgrass cross over the bar as West Ham sensed a way back into the encounter, while after Felipe Anderson had to limp out of the action in the 66th minute, Ederson kept out efforts by Javier Hernandez and Lanzini.
However, West Hams hopes of a comeback were dashed in the 75th minute when Sterling chipped the ball over Fabianski, the goal standing after another VAR check.
City were awarded a spot-kick with four minutes left when Mahrez was fouled by Diop and, after Sergio Agueros first penalty had been saved, the Argentinian sent Fabianski the wrong way with his second effort after VAR had ruled the West Ham goalkeeper was not on his line when the initial kick had been taken.
Sterling completed his hat-trick in stoppage time, tucking the ball home at the near post to put more gloss on the rout.