Aaron Ramsdale gets the nod to start in goal, replacing Nick Pope, who started Saturday night's league defeat at Liverpool and also played in the first-leg defeat to Manchester City last month.
Sven Botman returns to the starting side and is set to play as part of a five-man defence that will also feature Malick Thiaw and Dan Burn at centre-half and Kieran Trippier and Lewis Hall in the wing-back positions.
Nick Woltemade is also back in the starting XI for the first time since the Champions League draw in Paris St Germain, with Eddie Howe changing tack from the weekend, when Anthony Gordon led the line at Anfield. Gordon remains in tonight's side, but is expected to play on the left-hand side.
Anthony Elanga and Harvey Barnes drop out of the team that kicked off Saturday's defeat to Liverpool.
There is no Erling Haaland in Pep Guardiola's Manchester City side, with Omar Marmoush set to lead the line for the home side ahead of Phil Foden, Tijani Reijnders and Antoine Semenyo, who fill the attacking-midfield roles.
MAN CITY (4-2-3-1): Trafford; Nunes, Khusanov, Ake, Ait-Nouri; Gonzalez, O'Reilly; Semenyo, Reijnders, Foden; Marmoush.
Subs: Donnarumma, Dias, Haaland, Cherki, Rodri, Nypan, McAidoo, Alleyne, Lewis.
NEWCASTLE (5-4-1): Ramsdale; Trippier, Thiaw, Botman, Burn, Hall; Willock, Ramsey, Tonali, Gordon; Woltemade.
Subs: Pope, Wissa, Barnes, Osula, Elanga, J Murphy, A Murphy, Shahar, Neave.