The Gunners have fallen away from their rivals for Champions League qualification following defeats at Liverpool and West Bromwich Albion, and will have to overcome the uncertainty which surrounds their manager's future.
City, meanwhile, have improved domestically, but were held to a 1-1 home draw by Liverpool last time out. Pep Guardiola's side have won their last three league fixtures away from home against West Ham, Bournemouth and Sunderland.
What time is kick off?
The match will kick off at 4.00pm on Sunday 1 April.
A surprise early defeat, such as 2013/14's to Aston Villa or 2015/16's to West Ham United, makes July's Emirates Cup win seem like a distant memory.
Impressive win against top club
A promising win against a title rival, like last season's 3-0 victory over Manchester United or this season's win over Chelsea, has the Emirates hoping for the best again.
Injuries start to mount up
However, a long queue starts to form outside the treatment room. Key players, as well as regular absentees, tend to be the victims.
November curse strikes again
Arsene Wenger's side then begin to unravel in November, with the curse kicking in after an away defeat against one of the top flight's lesser lights. It's around now that the already-faint hopes of a title challenge start to fade.
Champions League elimination
The most predictable part of it all comes in February, with Champions League elimination, usually to Bayern Munich, Barcelona or Monaco, if they are really unlucky.
Title hopes finally killed off
A heavy, signature defeat to a fellow top six side puts paid to any lingering hopes of a title challenge in late February or March. 2013/14's 6-0 reverse at Chelsea, Arsene Wenger's 1,000th game in charge, is perhaps the most memorable example.
Strong rally to finish
The pressure is off, time to turn the style on. A rally at the tail end of the season does wonders for Arsenal's league standing, but little to combat allegations of flakiness.
Arsene has his 'trophy'. Champions League football is coming to the Emirates again next year. What more could the fans want?
Where can I watch it?
It will be shown live on Sky Sports 1, with highlights aired on BBC One at 10.30pm.
Past three meetings...
Manchester City 2 (Sane, Sterling) Arsenal 1 (Walcott)
Premier League, December 2016
Manchester City 2 (Aguero, De Bruyne) Arsenal 2 (Giroud, Sanchez)
Premier League, May 2016
Arsenal 2 (Walcott, Giroud) Manchester City 1 (Toure)
Premier League, December 2015