The Citizens start the game top of the table by just one point, with the Reds close behind and preparing to launch a title challenge themselves.
Pep Guardiola and Jurgen Klopp have had plenty of title fights across the years, and this season could be another one.
And the eventual winner might look back at this game as a huge turning point in the season.
Man City vs Liverpool: How to watch
This Premier League clash is set to take place on Saturday, November 25.
Kick-off at the Etihad is scheduled for 12:30pm.
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The match will be streamed on Sky Sports Main Event and Sky Sports Premier League, with their coverage set to start at 11am.
Sky Go customers will be able to stream the game through their laptops or mobile devices.
Alternatively, fans can purchase a NOW TV membership, with one-day passes starting at £11.98 or a monthly subscription for £34.99.
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Man City vs Liverpool: How to listen
talkSPORT will have live and exclusive commentary from Manchester.
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Your host will be Reshmin Chowdhury, with commentary coming from Sam Matterface, England icon Stuart Pearce, and former Wales striker Dean Saunders.
talkSPORT.com will also be running a live blog to keep you up to date with all of the action.
To tune in to talkSPORT or talkSPORT 2 through the website, click HERE for the live stream. You can also listen via the talkSPORT app, on DAB digital radio, through your smart speaker and on 1089 or 1053 AM.
Man City vs Liverpool: Team news
The hosts have picked up several injury concerns over the international break.
Erling Haaland has a twisted ankle but is expected to be fit to face Liverpool.
Rodri, Mateo Kovacic, Matheus Nunes, Ederson, and Nathan Ake will all face late fitness tests.
But Kevin De Bruyne, Sergio Gomez and John Stones are out with long-term injuries.
Meanwhile, the Reds will be without Andrew Robertson due to a dislocated shoulder.
Thiago Alcantara and Stefan Bajcetic remain on the sidelines.
But Klopp will hope Joe Gomez and Ryan Gravenberch are fit after picking up minor niggles.
Curtis Jones and Ibrahima Konate will also be pushing to be involved.
Man City vs Liverpool: What has been said?
Oasis co-founder and huge Man City fan Noel Gallagher believes Liverpool are City's closest contenders.
Speaking on talkSPORT Drive, he said: "I think it's probably between City, Liverpool and Arsenal.
"I'd probably whittle that down to Liverpool towards the end because when Liverpool get towards the finish line, they've always pushed us all the way until the last day."
However, he's fuming that the game is at 12:30.
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He said: "The 12:30 kick-off is set up to benefit people in other parts of the world. Liverpool have got a lot of fans in Southeast Asia, and I would imagine there's someone sitting there thinking when Liverpool play half 12, the global ratings go through the roof.
"It's one of the biggest fixtures in England, and we're not going to see the best of the two teams; lord knows who's going to turn up injured."