The game will be played at Hillsborough during the week commencing 2 March.
City have played the Owls in the FA Cup on several occasions and have never lost.
The first meeting was at Hyde Road, with City winning 3-0.
In 1934, on the way to winning the FA Cup, City held the Owls 2-2 at Hillsborough before winning he replay 2-0 at Maine Road.
It would be 73 years before the next meeting, with City again drawing at Hillsborough (1-1) before edging the replay at the Etihad 2-1.
In 2015, two James Milner goals eased City into the next round after a 2-1 win at the Etihad.
There will be no replay and if the teams are level after 90 minutes, there will be extra time and if necessary, penalties to determine a winner on the night
Ticket details and the date of the fixture will be released in due course.
Full draw:
Sheffield Wednesday v Manchester City
Reading or Cardiff v Sheffield United
Chelsea v Shrewsbury Town or Liverpool
West Brom v Newcastle or Oxford
Leicester v Coventry or Birmingham City
Northampton or Derby v Manchester United
Southampton or Spurs v Norwich City
Portsmouth v Bournemouth or Arsenal
Tickets for Wednesday’s Carabao Cup semi-final, second leg against Manchester United can be purchased here
Tickets for the Champions League, Round of 16 second leg versus Real Madrid can be bought here-
Fans can sign up to a 30-day free trial for City+, after which the cost will be just £1.99GBP/per month.
For more information, visit https://www.mancity.com/City+
