The two sides have developed a fierce and bitter rivalry over the past decade, regularly pushing each other to greater heights and battling for Premier League titles under respective managers Jurgen Klopp and Pep Guardiola.
There is a new era underway at Anfield, though, and Arne Slot's side have surged eight points clear of the defending champions at the top of the table after only 12 games.
Victory this weekend would fire the Reds 11 points clear of Man City, surely all but eliminating them from the title race by the beginning of December, making Sunday's showdown a potentially pivotal contest for the 2024-25 campaign.
With Liverpool making one of their best starts to a season ever and Man City suffering their worst run of form since the Abu Dhabi takeover, the Sports Mole team discuss who they believe will come out on top at Anfield.
Barney Corkhill - Liverpool
There is the nagging concern for Liverpool that, if any game could jolt Man City out of their unprecedented slump, it will be a match against Liverpool in which defeat would rule them out of the title race.
That said, Liverpool should feel more confident going into this match than they have any game against Man City in the Pep Guardiola era.
The Reds are absolutely flying that the moment - the performance against Southampton last weekend was complacent, but there is no chance that complacency will creep in again for a match of this magnitude, and after their statement win over Real Madrid in midweek, Arne Slot's side are going from strength to strength.
Contrast that with Man City, who have not only been on a dreadful run of results, but also a dreadful run of performances; the way the likes of Sporting Lisbon, Tottenham Hotspur and Feyenoord ripped through them should have Liverpool licking their lips.
Man City have conceded two or more goals in six straight games for the first time since 1963; Liverpool have scored two or more goals in seven straight games.
With players like Erling Haaland and Kevin De Bruyne, and one of the greatest and most ingenious managers of all time leading them, Man City can never be ruled out, and Ibrahima Konate's injury is a big blow for the hosts.
However, they have seriously struggled at Anfield even at their very best, and the home crowd will be baying for blood given the situation both teams find themselves in, what is at stake and the prospect of dealing an enormous psychological blow to a team who have been their biggest rivals in recent years.
Everything points to a Liverpool win and, barring a sudden Man City turnaround or a Guardiola masterstroke - which is by no means out of the question - this has the potential to get very messy for Man City.
I wouldn't be surprised to see Liverpool win big.
Ben Knapton - Liverpool
From the perspective of an Arsenal fan, both teams will lose. From the perspective of an impartial neutral, Man City will lose.
I wondered whether Liverpool's slightly lethargic display at Southampton would be a precursor to a downward spiral after such a scintillating start under Arne Slot, but they quickly proved me wrong against Real Madrid. Admittedly an injury-hit Real Madrid, but 15-time and current Champions League holders Real Madrid nonetheless.
A confidence-sapped Man City can take a bit of encouragement from Liverpool's recent defensive injury blows, but Ryan Gravenberch and Alexis Mac Allister should dominate the midfield battle with ease, and getting past an inspired Caoimhin Kelleher is no mean feat. At the other end, Mohamed Salah vs. an off-colour Josko Gvardiol has the potential to be a downright humiliation.
Arne's Anfield should be rocking by full time, and even Man City's customary end-of-season surge will surely not be enough for a fabulous fifth title in a row if they fall 11 points behind on Sunday.
Oliver Thomas - Liverpool
Over the last month, Manchester City have looked increasingly incapable of not just defending their Premier League title, but defending full stop. Not since Pep Guardiola's first season at the club in 2016-17 have they looked so vulnerable.
Tuesday's capitulation against Feyenoord was arguably a more damaging result from a mental standpoint than any of their previous five defeats. The Citizens are indeed both mentally and physically frail at present amidst a well-documented injury crisis, and the fact that they are being carved open at the back far too easily on several occasions is a real concern.
An in-form and confident Liverpool outfit, who have won their last six games on the spin, will be licking their lips at the prospect of capitalising on Man City's recently-exposed flaws and moving 11 points clear at the summit with a statement victory.
Man City's alarming slump surely cannot continue for much longer, but they have only won one of their last 21 league visits to Anfield and it is difficult to back against Arne Slot's side on Sunday.
Andrew Delaney - Liverpool
Even at the best of times, Pep Guardiola has struggled to beat Liverpool, never mind when they are in the middle of the biggest crisis they have faced in years.
Not only that, Liverpool are among the very best sides in Europe at present, and they have not lost against City at home in front of a crowd since 2003! Arne Slot's men will be at least nine points clear come Sunday evening.
Jonathan O'Shea - Liverpool
As it has been more than a month since Manchester City last did what they've done so frequently for over a decade - win - the pressure is all on the defending Premier League champions. With such a substantial cushion, Liverpool have less to lose - particularly as they weren't expected to be in this position.
Given their strength and confidence in the final third, Arne Slot's men can get the better of an ailing City defence and stretch their lead at the top. Liverpool 2-1 Man City.
Sam Varley - Liverpool
Given the two sides' contrasting momentum abs with the hosts seamlessly taking to life under Arne Slot, I envisage another Reds win at Anfield.
The loss of Rodri has already proved to be particularly costly for Manchester City and could leave them exposed to Liverpool's threats on the counter. Liverpool 2-0 Man City.
Lewis Nolan - Liverpool
Liverpool should be considered strong favourites heading into their clash against Manchester City, and backed by the power of the Anfield crowd, they should be confident of condemning Pep Guardiola's vulnerable side to a sixth defeat in seven games.
Given City's struggles at both ends of the pitch, there is a real possibility that Arne Slot's team overpower, outrun and possibly humiliate their rivals, effectively knocking them out of the title race. 3-0 to Liverpool.
Tom Humphrey - Liverpool
I think Liverpool will win this game. It is tough to look past the Reds when you compare the recent form of the two sides.
With it being at Anfield, a ground where Pep Guardiola's side have struggled at the best of times, it is one of the worst fixtures City could wish for right now.
Anthony Nolan - Liverpool
Liverpool appear to be in inspired form under Arne Slot and have only lost one game this season, while Manchester City seem to be spiralling having failed to win any of their last six matches.
All of the momentum is with Liverpool at the moment, and when combined with the hostile reception City can expect at Anfield on Sunday, it is hard to see anything but a dominant win for Liverpool. Liverpool 3-1 Manchester City.