Manuel Pellegrini's side has scored a whopping 57 goals this season and knows that victory over Alan Pardew's Magpies will elevate it to the top of the Premier League.
City, which sits second ahead of Saturday's fixtures, has an outstanding record against Newcastle in recent times, its last defeat coming in 2005 at St James' Park when a goal from Michael Owen gave the Tyneside club a 1-0 win.
Since then City has continually piled misery on Newcastle and will be confident of taking all three points from a team it has already beaten twice so far this season.
Manuel Pellegrini got his reign at the Etihad Stadium off to a flying start with a 4-0 home victory over Alan Pardew's side in his first game in charge, although the 2011-12 Premier League champion was made to work harder for a 2-0 League Cup triumph at Newcastle in October.
Victory this weekend would see City leapfrog leader Arsenal, which is not in action until Monday.
Striker Sergio Aguero is again set to miss out because of a calf injury, but City has been handed a boost with the news that Yaya Toure, Jesus Navas and Micah Richards are all fit to play.
The presence of Toure could be key to City's fortunes. The Ivory Coast midfielder has brushed off the ankle injury he sustained in Wednesday's 6-0 Capital One Cup win over West Ham and will be targeting more goals after scoring four times in his last four Premier League games against Newcastle.
Mathieu Debuchy serves the second game of a three-match ban for Newcastle, who will also be without captain Fabricio Coloccini (knee) as it aims to avoid a fourth consecutive defeat.
A win for Newcastle could see the Magpies move above City's local rival Manchester United and the hosts will be encouraged by the prospective returns of midfielder Yohan Cabaye and goalkeeper Tim Krul, who both missed the 2-1 FA Cup loss to Cardiff City.
However, Pardew may be forced to reshuffle his defence further due to a thigh injury that could keep left back Davide Santon out of action.
Pellegrini's side have scored 57 goals in 20 league matches, but only a third of those have come on the road.
Newcastle is seeking a first home clean sheet since early November, when Chelsea was beaten 2-0.