The Reds have tended to be a kryptonite for City in recent seasons, especially at home, while Reds manager Jurgen Klopp has enjoyed playing that role against opposite number Pep Guardiola for quite a while now.
But it’s the players who execute the two coaches’ clashing gameplans. Here’s a look at the key battles that will determine the outcome.
Roberto Firmino v Sergio Aguero
Roberto Firmino hasn’t been in great scoring form of late.
He only has three goals this season, two in the league. In fact, when it comes to finding the back of the net, though he finished seventh in last season’s scoring standings it was with a merely respectable tally of 15.
It didn’t matter because Firmino’s play was helping Mohamed Salah score for fun. But the Egyptian’s form hasn’t hit last season’s heights, which has the added effect of bringing his team-mate’s scoring record into the spotlight.
As long as Liverpool keep chugging along, it won’t matter who scores the goals. But they could still do with their central striker finding the net more regularly.
No such problems over at City, where Sergio Aguero shows no signs of slowing down, just over a year after his future at City was in doubt following speculations that Guardiola didn’t consider the striker the ideal man for his system.
That argument has disappeared completely following a season in which his goals delivered a league title, and he’s started this campaign with six goals across competitions.
Five of those have come in the league, including a hat-trick against Huddersfield. He’s scored in three-straight games, though given that those were all one-goal performances, he’s probably due a brace or another hat-trick against Liverpool.
James Milner v David Silva
James Milner might be 32, but these days it seems like his best is still being unlocked, or just getting better and better. His ability to find a team-mate simply by being in the right place to play the right pass is among the best in the league – he’s currently tied for seventh in the Premier League’s all-time assist charts with 80, and he could easily end up becoming just the fourth man to 100.
Finally being consistently played as a midfielder since last season, he’s now a guaranteed starter in a team that bought two midfielders this summer. Says it all.
Unlike Milner, fellow 32-year-old David Silva has been far more feted in terms of overall recognition, though Milner has previously won a PFA award (2010 Young Player of the Year). Hopefully one day Silva equals that tally, because there is now a serious argument to be made that he’s the best midfielder in Premier League history.
It also does seem like Silva, too, is only getting better with age, like his former team-mate, and this season he’s been crucial to ensuring Kevin De Bruyne‘s injury-enforced absence hasn’t been felt at City. This fixture could throw up a midfield duel for the ages.
Andy Robertson v Kyle Walker
With each passing Andy Robertson performance, the £8 million Liverpool paid Hull City for him last summer seems less like mere daylight robbery and more a legendary heist deserving of a movie, perhaps with an all-star ensemble cast playing the much-derided Anfield transfer committee.
In a poor Liverpool display against Napoli in midweek, the left-back was one of the few shining lights. Now it’s the fearsome City attack he has to stop, but who would bet against him?
Part of that attack includes City’s own full-back, as Kyle Walker has cemented his reputation as the best attacking right-back in the league. Where once he was almost pure pace, now he’s got the skill, vision, and passing range to match, as Guardiola has molded him into the prototypical modern full-back.
He still uses that pace as a crutch to bail him out of the occasional defensive lapse, something that will be tested by Robertson’s own attacking ability. It should be a fascinating battle between the two players.
Tottenham boss Mauricio Pochettino suggested he was frustrated with Belgium manager Roberto Martinez for publicly discussing Jan Vertonghen’s hamstring injury before Spurs had the chance.
Martinez announced his Belgium squad on Friday and said Vertonghen would miss the next two international breaks, this month and in November.
But Pochettino, speaking later to preview Saturday’s Premier League clash with Cardiff, insisted Spurs do not yet know the full extent of Vertonghen’s injury, with a scan scheduled for Monday.
“We’ll see. It was not a good injury,” Pochettino said.
“We’re so disappointed with that. We’ll see if it’s six weeks or less.
“We hope as soon as possible it can be fixed but we cannot guess.”
Pochettino said it was Spurs’ responsibility to discuss injuries.
The Argentinian added: “Before my press conference you knew about the Vertonghen situation because Roberto told the media in Belgium before us.
“But in the end it’s our player, our Tottenham player. Our Tottenham employee. We arrived here and we needed to explain.
“It’s difficult. They need to call us. If they call us, we are more than open to talk – and give our opinion. But if they don’t call, our door is always open to receive (a call).
“The players are here every day and in the end our job is day-by-day and for them it’s every month.
“I don’t want to create a problem but that is the normal behaviour – that the national team calls you.
“Not that you call and say ‘be careful with this player or that player’. It’s like you don’t want the player to go to the national team.”
Vertonghen sustained the injury in a challenge with Huddersfield striker Laurent Depoitre in Spurs’ 2-0 win but played on until half-time, not realising the severity of the issue.
Pochettino added: “It’s difficult to assess during the game because he didn’t realise how it was and he only felt a big knock from the striker and he thought it was a dead leg.”
Spurs had rested the defender, along with Harry Kane, Kieran Trippier and Danny Rose, for the Carabao Cup clash with Watford, after the quartet’s World Cup exertions.
But Vertonghen’s injury in the next game means he joins Christian Eriksen (abdominal), Mousa Dembele (thigh), Dele Alli (hamstring) and Serge Aurier (thigh) in being absent.
Spurs lost 4-2 to Barcelona on Wednesday night and are seeking a third successive league win on Saturday against Neil Warnock’s newly-promoted Cardiff.
Pochettino says the outside perception is Saturday should be an easy game for Spurs, but his players must play at the same level as they did against Barca.
“The most difficult game is the game that everyone believes, outside of the team, that you must win,” Pochettino added.
“For us it’s so important to be motivated at the same level. If not we’re going to struggle.”
Pochettino added that the playing surface at Wembley is not as bad as it looks.
He added: “I don’t want to complain. Maybe from outside it looks not good. Inside it is OK. It’s possible to play football.
“If we don’t play well, it’s not because of the pitch. It’s maybe a lack of quality, but not because of the pitch.”
The 18-year-old scored his first senior goal for the Gunners as they beat Qarabag 3-0 in their Europa League Group E clash in Baku on Thursday night.
Smith Rowe struck Arsenal’s second and killed off any chance of a comeback from the hosts, as Sokratis Papastathopoulos and Matteo Guendouzi also grabbed their maiden goals for the club.
An Under-17 World Cup winner with England last summer, Smith Rowe has now made two starts this season – one in the Carabao Cup win over Brentford and here against Qarabag.
He is yet to feature in the Premier League but went on Arsenal’s pre-season tour to Singapore before deciding to stay and fight for first-team appearances rather than leave on loan.
Asked whether it was a gamble not to move away in the summer, Smith Rowe said: “It was a chance I took and I am happy I have taken it because now he (head coach Unai Emery) is really happy with me, he helps me a lot and to get the chances I am getting now is crazy.
“Now I am really enjoying it. I was enjoying it before but I am getting chances and I am so grateful that the gaffer has got faith in me. I just want to keep improving and keep getting minutes.”
Emery praised Smith Rowe’s mentality after the win at the Baku Olympic Stadium, while the player said he was keen to stay put because he wanted to work under the Spaniard.
Although he has made three appearances so far, Smith Rowe revealed he has yet to be welcomed into the first-team changing room at the club’s London Colney training base.
“I am not actually in the changing room at the training ground,” he said.
“But when I come to games, I look around and can’t believe I’m here. It is still surreal. I change separately, find out about 10 minutes before, just run over and train.”
Smith Rowe has seen his fellow England Under-17 World Cup winner Jadon Sancho called up into the senior squad this week after starring at Borussia Dortmund, with another promising youngster in Mason Mount also included.
Three Lions boss Gareth Southgate is willing to give young players a chance and Smith Rowe now harbours ambitions to get there himself.
“The England youngsters are a very talented bunch of lads,” he added.
“I think in the future there will be a lot of youngsters going through to the first team. Hopefully one day I can be part of the team.
“I’ve played with Sancho. I haven’t played with Mason before. But he is a great player as well.
“It just shows that he (Southgate) wants to play the youngsters and England are changing their way of playing now which is getting really good.”