The Hammers are big underdogs, with some bookmakers offering as much as 13-1 for an away win after Manuel Pellegrini's side's perfect start to the new Premier League season.
But Slaven Bilic's men have made a decent start too, their best for seven years no less, and already have the scalps of City's supposed title rivals Arsenal and Liverpool from their two away matches so far.
City were late 1-0 winners at Crystal Palace last time out, but lost 2-1 to Juventus in the Champions League midweek, while West Ham comfortably saw off Newcastle United 2-0 on Monday.
History books don't make good reading for Irons
It is not just the odds that are stacked against the East Londoners when they pitch up at the Etihad, but the history books too.
Of 49 matches between the two sides in Manchester, the Blues have won 33, three times that of West Ham's 11, while there have been five draws.
Sky have chosen to cover the game live on Saturday evening, and it is easy to see why.
Not only have West Ham already pulled off some away shocks and City have their 100% winning start on the line, but the history books promise goals too.
In the 49 games in Manchester there have been 163 goals, 101 for City and 62 for the Hammers.
While West Ham fans have nightmarish memories of a League Cup semi-final trip to the Etihad in the 2013/14 season, which they lost 6-0.
But their biggest ever league defeat on the road to the Blues came in the 1974/1975 season, when John Lyall's side lost 4-0.
The Hammers put it behind them, though, going on to lift the FA Cup for the second time with a 2-0 victory over Fulham at the end of that season.
The last time the two sides met came back in April when City ran out comfortable 2-0 winners at the Etihad.
They played for both
A number of notable players have played for both West Ham and Manchester City over the years, and here we take a look at some of the prestigious names on that list.
Ian Bishop, Trevor Morley, David Cross, Craig Bellamy, Steve Lomas, Paulo Wanchope, David James, Wayne Bridge, Mark Ward, Trevor Sinclair, Marc Vivien-Foe, Stuart Pearce, Martin Samuelsen, Kevin Horlock, Frank Lampard, Carlos Tevez.