Three points in Manchester would take Chelsea to eight consecutive league victories for the first time since 2010.
City are one point behind Chelsea heading into the first meeting this season between two teams who have quickly emerged as leading title contenders under their new managers.
While City featuring in a title battle only five months into Pep Guardiola's reign is hardly a surprise given the club's financial muscle and their Spanish manager's impeccable CV, Chelsea's presence at the top of the table is more unexpected.
The Blues were in turmoil last season after Jose Mourinho was sacked, but former Italy and Juventus coach Antonio Conte has teased out renewed focus and passion from a squad of fragile egos and the results have been impressive.
Three points in Manchester would take Chelsea to eight consecutive league victories for the first time since 2010, but City have lost just one of their last 15 league games and have a point to prove about the rivals' differing schedules.
While third placed City have had the pressure of trying to qualify from a tough Champions League group, Chelsea have enjoyed the luxury of extra rest due to their failure to quality for European competition.
"We'll have played eight more games -- terrible games -- in the Champions League than Chelsea and Liverpool and we are there," Guardiola said.
"That's why the first part of the season is so satisfying. To still be with Liverpool and Chelsea when they don't play in Europe is good for us."
However, Chelsea goalkeeper Thibaut Courtois played down the title implications of the result on Saturday.
While beating City would be a morale boost, Courtois says it is just as important for Chelsea to show their ruthless streak in the following fixtures against West Bromwich Albion, Sunderland, Crystal Palace, Bournemouth and Stoke.
"Now we are going to Man City to try and get another result, and then after it the next away games are at Sunderland and Crystal Palace, and it is games like those that decide if you are going to be champions or not," Courtois said.
"You can win big matches even if you're not having a good season, because it is a big match or a derby, but it is the smaller matches against difficult adversaries that you will see if you are going to be champions or not."
A draw at Eastlands would give second placed Liverpool the chance to go top if they win at Bournemouth on Sunday.
Jurgen Klopp's side are unbeaten in their last 11 league matches and the German said: "It's a good moment, but it's difficult too because there's a lot of work to do and a lot of games to play.
"We go now to Bournemouth, a small stadium, but very intense with a good team."
Arsene Wenger is confident fourth placed Arsenal will get back on track after their surprise League Cup exit when they face West Ham.
Wenger's side were beaten 2-0 at home by Southampton in the quarter-finals on Tuesday, while West Ham also crashed out of the competition with a 4-1 thrashing at Manchester United.
Looking for a quick recovery, Wenger is confident Arsenal will banish the memory of the Cup disappointment, which ended their 19-game unbeaten run in all competitions.
"I don't think I can moan about the momentum in the Premier League," he said.
"I knew that in the League Cup that could happen, but it was more disappointing to lose the game than the run we have. We want to keep the run in the Premier League going now."
Manchester United travel to Everton aiming to maintain the momentum of their midweek victory.
Mourinho's team are 11 points behind Chelsea after winning just one of their last seven league games, but United midfielder Michael Carrick hasn't given up hope of a successful season.
"You can't beat that buzz of winning a big game," Carrick said. "That is what keeps you going, having success and winning trophies."
Fixtures (1500 GMT unless stated)
Crystal Palace v Southampton, Manchester City v Chelsea (1230 GMT), Stoke v Burnley, Sunderland v Leicester, Tottenham v Swansea, West Brom v Watford, West Ham v Arsenal (1730 GMT)
Bournemouth v Liverpool (1330 GMT), Everton v Manchester United (1600 GMT)
Middlesbrough v Hull (2000 GMT)