Manuel Pellegrini's side will begin their challenge to retain the trophy with a home tie in the competition against the Championship outfit.
The clash sees the two teams lock horns for the first time since January 2007.
On that occasion, goals from Stephen Ireland and Darius Vassell earned a 2-1 win for Stuart Pearce's squad in an FA Cup replay after the reverse fixture ended in a 1-1 draw nine days earlier.
City have faced the Owls in the League Cup before back in 1979. Again, the Manchester outfit required a replay to progress with both encounters ending in the same scorelines of 1-1 and 2-1.
Sheffield Wednesday reached the third round of this year's competition having defeated Notts County 3-0 at Hillsborough and most recently, Premier League side Burnley 1-0 at Turf Moor.
This tie will take place on Wednesday 24 September at 19:45
Ticket details will be revealed right here on mcfc.co.uk in due course...