The England international returns to the heart of midfield to likely partner Daichi Kamada in the central areas, with Jefferson Lerma the player to make way; he moves to the bench.
Otherwise, Palace are unchanged from the side which battled through to the fourth round of the Cup in midweek.
That match saw a first Palace goal for Eddie Nketiah, who scored twice for Arsenal against Manchester United last year, and a second strike of the season for Ebere Eze, who also starts this afternoon.
Recent arrival Matt Turner and Academy prospects Franco Umeh and Asher Agbinone are potential debutants this afternoon.
Palace: Henderson (GK), Richards, Lacroix, Guéhi, Muñoz, Wharton, Kamada, Mitchell, Eze, Mateta, Nketiah.
Subs: Turner (GK), Ward, Clyne, Hughes, Lerma, Schlupp, Sarr, Umeh, Agbinone.
Manchester United: Onana (GK), Mazraoui, Martinez, De Ligt, Dalot, Mainoo, Eriksen, Ama, Fernandes, Garnacho, Zirzkee.
Subs: Bayindir (GK), Evans, Maguire, Casemiro, Ugarte, Mount, Antony, Hojlund, Rashford.