The midfielder has a minor foot problem and will not be risked by manager Alan Pardew, who is likely to use the depth of his squad as he attempts to balance the demands of the cup competition and the Barclays Premier League.
That could mean further action for summer signing Demba Ba, who has played just a single half to date this season, and a competitive debut for Sylvain Marveaux, while youngsters Haris Vuckic and Sammy Ameobi may also come into the mix.
New signing Oliver Norwood will go straight into Scunthorpe's squad.
The midfielder has joined the Iron on loan until January from Premier League giants Manchester United.
Manager Alan Knill will be without defender Paul Reid who will miss the visit of the Magpies with a groin injury.
The centre-back had been struggling with the problem and had to come off at half-time in the 2-2 draw with Charlton on Saturday.
Reid's replacement was Niall Canavan and he looks set to slot in alongside Michael Nelson from the start.
Striker Jordan Robertson is out of action until December with a broken ankle while right-back Cliff Byrne is another long-term absentee with a back problem.
Newcastle (from): Krul, Harper, Simpson, Ryan Taylor, Ferguson, Coloccini, Steven Taylor, Williamson, Tiote, Cabaye, Gutierrez, Marveaux, Obertan, Gosling, Smith, Abeid, Ba, Shola Ameobi, Lovenkrands, Best, Vuckic, Sammy Ameobi.