Jamaal Lascelles and Jacob Murphy replace Tino Livramento and Miguel Almirón for the 17:30 GMT kick-off at the Etihad Stadium.
Gordon came off in the first half at Chelsea on Monday night, but in a big boost to both Howe and to England boss Gareth Southgate, who handed him a first senior international call-up this week, he escaped serious injury.
The introduction of Lascelles, who will make his 250th appearance in all competitions for the Magpies, suggests that the Magpies will switch to a back five against the cup holders. Livramento, who has started the last two games, is not part of the squad after picking up an ankle knock at Stamford Bridge.
Martin Dúbravka starts in goal, with Lascelles joined by Sven Botman and Fabian Schär in defence. Dan Burn is also named in the starting XI, with Jacob Murphy an option for right wing-back should that be the tactic employed.
Alternatively, the versatile Murphy could be utilised on the flanks along with Gordon. Sean Longstaff, Bruno Guimarães and Joe Willock make up the midfield, with Alexander Isak - who scored the winner when the two sides met the in the Carabao Cup earlier this season - up front.
Almirón is on the bench, along with Emil Krafth, Lewis Hall, Matt Targett, Paul Dummett, Matt Ritchie, Lewis Miley and Elliot Anderson. Loris Karius is United's back-up goalkeeper.
Newcastle United: Martin Dúbravka, Sven Botman, Fabian Schär, Jamaal Lascelles (c), Dan Burn, Bruno Guimarães, Sean Longstaff, Joe Willock, Jacob Murphy, Alexander Isak, Anthony Gordon
Substitutes: Loris Karius, Emil Krafth, Lewis Hall, Matt Targett, Paul Dummett, Matt Ritchie, Lewis Miley, Elliot Anderson, Miguel Almirón