The former England captain called time on his nine-year stint at Old Trafford this summer in order to return to his boyhood club, having become United's all-time leading goal scorer during his time at Old Trafford.
Rooney is expected to lead the line this afternoon in what is expected to be a 5-3-1-1 formation for the Toffees, as Ronald Koeman makes two changes from the side that suffered a 3-0 home defeat to Tottenham Hotspur last weekend.
Having featured in the 3-0 loss at Atalanta in the Europa League on Thursday, Phil Jagielka earns a recall in the heart of the defence this afternoon alongside Michael Keane and Ashley Williams, with Cuco Martina on the right and Leighton Baines on the left, while Jordan Pickford is back between the sticks.
Morgan Schneiderlin is also in action against his former side, partnering Idrissa Gueye and Tom Davies - in for Davy Klaassen - in midfield, with Gylfi Sigurdsson assisting Rooney in the attacking threat.
For the visitors, Jose Mourinho makes five changes following the 3-0 Champions League victory over Basel on Tuesday and three alterations to the starting XI from the 2-2 draw at Stoke City in the league eight days ago.
Romelu Lukaku retains his place up front, with Juan Mata, Henrikh Mkhitaryan and Marcus Rashford providing attacking assistance. Paul Pogba limped off in midweek and now faces a spell on the sidelines, while Ander Herrera and Anthony Martial start among the substitutes.
Ashley Young keeps his place in the defensive line, with Matteo Darmian on the bench, as Eric Bailly and Phil Jones resume their partnership at centre-back after both were suspended for the Basel win.
Manchester United: De Gea; Valencia, Bailly, Jones, Young; Matic, Fellaini; Mata, Mkhitaryan, Rashford; Lukaku
Subs: Romero, Darmian, Smalling, Carrick, Herrera, Lingard, Martial
Everton: Pickford; Martina, Keane, Williams, Jagielka, Baines; Schneiderlin, Gueye, Davies; Sigurdsson; Rooney
Subs: Stekelenburg, Ramirez, Mirallas, Klaassen, Besic, Calvert-Lewin, Holgate
Keep up with all of the action from Old Trafford this afternoon with Sports Mole's live text commentary here.