Sergio Aguero, Leroy Sane and Raheem Sterling all start for Pep Guardiola's side who will be hoping to dump the Championship side out.
In defence, Claudio Bravo returns in goal with John Stones partnering Nicolas Otamendi in central defence and Gael Clichy and Pablo Zabaleta the full-backs.
Elsewhere Aleix Garcia is handed a rare start while Kevin De Bruyne also features with David Silva on the bench.
Huddersfield meanwhile, currently third in the Championship, make nine changes to their side for the trip to the Etihad.
The winners of the tie face a quarter-final clash with Middlesbrough at the Riverside Stadium.
Man City: Bravo, Zabaleta, Clichy, Stones, Otamendi, Fernandinho, A. Garcia, De Bruyne, Sterling, Sané, Agüero.
Subs: Caballero, Sagna, Fernando, Navas, Delph, Silva, Iheanacho.
Huddersfield: Coleman, Whitehead, Hudson, Biling, Bunn, Holmes-Dennis, Cranie, Payne, Lolley, Quaner, Stankovic.
Subs: Ward, Smith, Hogg, Kachungga, Van La Parra, Wells, Hefele