After winning all three festive fixtures, City are level with Manchester United on 41 points at the top of the Premier League, with Arsenal third on 39.
Having not tasted success at the Gunners since 1975 and having lost 3-0 at home to them in October, victory would go a long way to convincing even City's most pessimistic fans that they are serious contenders to win the league for the first time since 1968.
"It seems ridiculous that we haven't won there since the 1970s but that has to end sometime," assistant manager Brian Kidd, who played for both clubs, told City's website.
"They beat us fair and square in the first game but I wouldn't change our squad for any other. I don't fear any team in the league."
"Now we want to play them with 11 men," said defender Jerome Boateng.
"I don't believe in bogey teams or jinxes and things like that I only look to the next game. That City have not won at Arsenal for a long time makes no difference to what might happen on Wednesday night.
United needed a late goal by Javier Hernandez to secure a 2-1 win at The Britannia in October and they are expecting another tough battle with Tony Pulis's physical side.
"They always have a go and you have to win that battle and earn the right to play," United midfielder Darren Fletcher said.
Chelsea, still reeling from conceding a stoppage-time equaliser in Sunday's 3-3 home draw with Aston Villa after scoring twice in the last six minutes, visit Wolverhampton Wanderers on Wednesday.
The champions' poor run, which has brought 10 points from the last 10 games, has seen them drop outside the top four and they now trail United by six points having played a game more.
