Although both are faltering in the Barclays Premier League title race, they possess some of the world's leading stars thanks to their vast spending power.
Ahead of the showdown, here's five big signings who proved their value in recent clashes between the sides.
Manchester City 1 Chelsea 0 (September 25, 2010) City and Chelsea splashed out an eye-popping ?200million between them last summer. But it was Carlos Tevez - bought for ?25m in 2009 - who scored a superb solo goal to seal the points. The striker had threatened to retire after the summer's World Cup, but his inheritance of the armband before this match - helped also by his healthy pay-packet - kept him at Eastlands.
Carlos' Way: Manchester City have already claimed Chelsea's scalp this season
Manchester City 2 Chelsea 1 (December 5, 2009) Emmanuel Adebayor has endured a rollercoaster career at City after signing in July 2009 for an ?24m from Arsenal. But the moody striker enjoyed a prolific start at Eastlands, scoring in his four first games. In this meeting, he cancelled out an early own goal that had gone in off his back with a close-range finish, before fellow summer arrival Tevez clinched the win.
Mind your back: Emmanuel Adebayor (centre) scored at both ends against Chelsea in 2009
Chelsea 1 Manchester City 0 (March 15, 2009) Chelsea had been beaten by City to ?32.5m Robinho in the summer, but they had other aces up their sleeves. Essien - who broke Drogba's transfer record at Chelsea when he signed for ?24.4m in 2005 - gave the Blues a huge boost in the title race after 13 minutes. The Ghana midfielder looked unstoppable on his first start since a cruciate knee ligament injury the previous September, and exploited a tired City to fire home from Frank Lampard's free-kick.
Driving force: Michael Essien proved the match-winner in 2009, firing in from Frank Lampard's free-kick
Manchester City 0 Chelsea 2 (April 5, 2008) Nicolas Anelka inflicted City's worst home defeat of the season after Chelsea bought him for ?15m in January 2008. A hapless Richard Dunne assisted in the humiliation when he diverted Anelka's cross to Michael Essien into his own net. Salomon Kalou dodged Joe Hart to add Chelsea's second and it took two excellent saves from the City keeper to stop Anelka making the defeat even costlier.
Hasn't got a Kalou: Chelsea's Salomon wrapped up the points in an easy win in 2008
Chelsea 6 Manchester City 0 (October 27, 2007) Having signed a new four-year deal at Chelsea in 2006, ?24m Didier Drogba feared the club was 'broken' following Jose Mourinho's exit a year later and said he wanted to leave. But he rallied under Avram Grant to show that money can soothe all kinds of wounds - scoring twice in the Blues' hammering of Sven Goran Eriksson's sorry side.
Taunt: Chelsea's Didier Drogba was keen to remind City fans of the score
Explore more:People: Robinho, Joe Hart, Michael Essien, Didier Drogba, Carlos Tevez, Emmanuel Adebayor, Richard Dunne, Frank Lampard, Nicolas Anelka, Sven Goran Eriksson, Jose Mourinho Places: Ghana