The Armenia international makes his first start since the 2-1 defeat to Manchester City in early September, and just his fifth appearance overall since joining in the summer.
Mkhitaryan takes his place in a much-changed United XI, showing a total of six alterations from the 1-1 draw with Arsenal here five days ago as Mourinho's men go in search of the win required to remain on course for progression from Group A.
Sergio Romero is also brought back into the first-team fold in place of the rested David de Gea, while Daley Blind and Luke Shaw return in the defence - a first appearance for the latter since being publicly criticised by his manager.
The other big news as far as the hosts are concerned is that skipper Wayne Rooney is also reinstated in the starting lineup, fielded in a three-man attacking midfield just off Zlatan Ibrahimovic, who is preferred to Marcus Rashford following his return from suspension.
Feyenoord are without a number of key players for the trip to Old Trafford, meanwhile, as Karim El Ahmadi, Terence Kongolo and Eric Botteghin all miss out through a mixture of suspension and injury, but Tonny Vilhena - the matchwinner in the reverse fixture - features from the off in midfield.
United, trailing their opponents by one point in the standings, face elimination from the competition this evening should they suffer defeat on home soil.
Manchester United: Romero; Valencia, Jones, Blind, Shaw; Carrick, Pogba; Mata, Rooney, Mkhitaryan; Ibrahimovic
Subs: De Gea, Rojo, Fellaini, Herrera, Lingard, Memphis, Rashford
Feyenoord: Jones; Karsdorp, Vd Heijden, Dammers, Nelom; Vilhena, Kuyt, Tapia; Elia, Jorgensen, Toornstra
Subs: Hansson, Woudenberg, Nieuwkoop, Vejinovic, Berghuis, Basacikoglu, Kramer
Follow all of the action as it unfolds with Sports Mole's live text coverage right here.