The game will be broadcast live on BBC One, with kick off at Hillsborough scheduled for 7.45pm.
Wednesday, managed by Garry Monk, currently sit 11th in the Championship and have beaten Brighton and QPR en route to the fifth-round stage.
Ticket details will be announced in due course.
Full draw:
Sheffield Wednesday v Manchester City
Reading v Sheffield United
Chelsea v Liverpool
West Brom v Newcastle
Leicester v Birmingham City
Derby v Manchester United
Spurs v Norwich City
Portsmouth v Arsenal
Tickets for the Champions League, Round of 16 second leg versus Real Madrid can be bought here.
And 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+