After barely seeing first-team action since moving to Old Trafford from Borussia Dortmund in the summer, the Armenia international will have the chance to shine in a match which United must not lose if they are to have any chance of progressing to the knockout stage of the competition.
Mkhitaryan has made just five appearances for United in his first three months at the club, with only a single start to his name, but joins Rooney and Juan Mata in supporting lone striker Zlatan Ibrahimovic against the Dutch club.
Shaw also starts on the left side of defence in a strong United team, who are desperate to grab a place in the Europa League knockout stages with just two games remaining.
Manchester United (@ManUtd) November 24, 2016
And Argentina No. 1 Sergio Romero earns a rare appearance replacing David de Gea between the posts, while Michael Carrick and Paul Pogba anchor the midfield.
The Spain international is on the bench, alongside Marcus Rashford who failed to earn a place in the first team for Thursday's encounter.
MAN UTD: Romero; Valencia, Jones, Blind, Shaw; Carrick, Pogba; Mata, Rooney, Mkhitaryan; Ibrahimovic. Subs: De Gea, Rojo, Fellaini, Herrera, Lingard, Memphis, Rashford.
FEYENOORD: Jones; Karsdorp, Dammers, Van der Heijden, Nelom; Tapia, Kuyt, Vilhena, Toornstra, Jorgensen, Elia. Subs: Hansson, Woudenberg, Nieuwkoop, Vejinovic, Berghuis, Basacikoglu, Kramer.