Carlo Ancelotti's men roared away from the pack by winning their opening five league games and outscoring some of the lesser lights in the division 21-1 but stumbled when they came up against their first major obstacle at Eastlands.
Arsenal also lost their unbeaten league record last week when they were surprisingly beaten 3-2 at home by West Bromwich Allbion.
Arsenal manager Arsene Wenger will hope for a vastly improved performance from his side who have lost their last four matches to Chelsea in FA Cup and League.
City outmuscled Chelsea in midfield with their powerful Dutchman Nigel de Jong giving a robust performance, but Arsenal's injury-prone and less robust players will have to chose another route.
The hugely talented Jack Wilshere has the gift of creating chances for the front men, but only Samir Nasri looks lethal in front of goal at present, although Marouane Chamakh is an increasing danger in front of goal.
It will suit Chelsea to sit back, absorb whatever Arsenal throw at them and attack on the break because although Arsenal play attractive, attacking football their defensive frailties -- especially in goal -- were easily exposed by West Brom.
Goalkeeper Manuel Almunia had a poor game and injured himself saving a penalty he conceded. The often-criticised Lukasz Fabianski replaced him for Tuesday's Champions League match against Partizan Belgrade and impressed, but he is always capable of a major gaffe.
The 25-year-old Polish international said: "I have never been bothered by the things said about me, I am always trying to focus on my job and my work. Now I am ready to play against Chelsea, so we will see if I do."
Chelsea recovered from their loss to City with a 2-0 victory over Olympique Marseille in the Champions League on Tuesday and if Ancelotti continues with the exciting Frenchman Gael Kakuta in attack, the Arsenal defence will have plenty to cope with.
However, Chelsea will still be without the injured Frank Lampard in midfield and Salomon Kalou up front.
Chelsea go into the derby as league leaders with 15 points from six games, followed by Manchester United (12), Arsenal (11) and Manchester City (11).
United's 1-0 win at Valencia in the Champions League on Wednesday will have boosted their self-belief after their 2-2 draw at Bolton Wanderers last week and they face a tricky visit to Sunderland, managed by their old player Steve Bruce, on Saturday.
Striker Wayne Rooney will be missing with an ankle injury, but the match could mark Rio Ferdinand's return to league action after he returned to the side on Wednesday for his second Champions League apppearance of the season after having missed the start of the league campaign through injury.
While Chelsea and Arsenal do battle at the top, Liverpool will be aiming to pull away from the other end of the table when they face Blackpool at Anfield.
Bottom-placed Everton will be looking for their first win of the season at Birmingham City and Manchester City
