Arsenal may be leading the way in the league, though City will be desperate to derail their rivals when it comes to the FA Cup.
Here, we take a look at the five main talking points ahead of Friday's encounter.
Who are the favourites?
Form points to Arsenal, who are five points clear at the top of the Premier League, but experience favours City. The Gunners have been outstanding this season, racing to 50 points in the opening half of their campaign and making an unexpected title charge they look increasingly likely to sustain. Yet City, consistently outstanding and highly successful in recent years, are unlikely to give up their crown without a fight. They are yet to meet this season, making this clash particularly intriguing.
Will both teams be at full tilt?
This is unclear. While this tie has all the ingredients of a classic, it remains to be seen how strongly managers Pep Guardiola and Mikel Arteta want to play it. Both have other priorities with Guardiola setting his sights on the elusive Champions League and Arteta bidding to end the Gunners' 19-year wait for a league title. Guardiola has pursued the domestic cups with vigour in the past, regardless of the aims in other competitions, but City's recent form has been patchy and it is uncertain which version of them will turn up. Arsenal's intensity could depend on how many changes Arteta makes.
What could the result mean for the title race?
As the sides have not yet faced each other this season, and with their first Premier League meeting just a few weeks away, it will be intriguing to see how they measure up to each other. Neither will want to overplay their hand but would undoubtedly relish the chance to land a psychological blow. Some of the individual battles - on the field and the touchline - could be fascinating, not least for how they could affect the plotting for future games.
How well do the managers know each others' thinking?
After three years working together at City, old master Guardiola and his former assistant Arteta seem unlikely to surprise each other if they stick to their usual gameplans. It will be interesting to see the line-ups and which players are deployed for certain roles, or if there is any tactical variance from the norm. Guardiola has won six of their seven meetings but Arteta prevailed in the 2020 FA Cup semi-finals and has a stronger team than previously.
What is the team news?
City have a near fully-fit squad after defenders John Stones and Ruben Dias recently returned to action after injury lay-offs. The only question mark is over England international Phil Foden, who was not involved at all against Wolves last weekend, with Guardiola saying he had a foot problem. Foden is actually a player in need of game time having been quiet since returning from the World Cup. Arsenal have no fresh injury concerns but Gabriel Jesus, Reiss Nelson and Mohamed Elneny remain on the sidelines.
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