The midfielder was replaced by Michael Carrick against Newcastle after just 66 minutes of play before losing his starting place altogether for the following games against Huddersfield and Sevilla.
He has been selected for United's league clash with Chelsea, however, alongside Scott McTominay and Nemanja Matic in what appears to be a 4-3-3 setup for Jose Mourinho's side.
Anthony Martial's return to the starting XI is another notable inclusion for the home side, with Juan Mata making way. The change gives Mourinho the opportunity to either start Martial on his favoured left side of attack and Alexis Sanchez on the right, or keep Sanchez on the left side and use the Frenchman from the less familiar right flank.
For Chelsea, Alvaro Morata returns to lead the attack, with Eden Hazard and Willian playing behind the Spain international.
He replaces Pedro in one of two changes from the side which drew 1-1 with Barcelona on Tuesday, with Danny Drinkwater replacing Cesc Fabregas in the other alteration for Antonio Conte's outfit.
For Morata it is a first league start in six weeks, providing him with the opportunity to break a two-month scoring duck.
Man Utd XI: De Gea; Valencia, Lindelof, Smalling, Young; McTominay, Pogba, Matic; Alexis, Lukaku, Martial. Subs: Bailly, Mata, Lingard, Carrick, Rashford, Shaw, J Pereira.
Chelsea XI: Courtois; Azpilicueta, Christensen, Rudiger; Moses, Drinkwater, Kante, Alonso; Willian, Morata, Hazard. Subs: Caballero, Fabregas, Pedro, Giroud, Zappacosta, Cahill, Palmieri.