Jose Mourinho has lived up to his word and kept his club captain out of side for the second consecutive game, having admitted that "he cannot afford to have a performance that is not really good."
Rooney, who appeared as a second-half substitute in Saturday's 4-1 win over Leicester, was always a doubt for the visit of Zorya after missing Tuesday's training session with a back problem.
Despite resuming light training on Wednesday, the 30-year-old forward has not been risked for the Group A clash.
Mourinho makes a total of four changes to the side which beat defending Premier League champions Leicester.
Sergio Romero, Timothy Fosu-Mensah, Marcos Rojo and Marouane Fellaini come in for David de Gea, Antonio Valencia, Daley Blind and Ander Herrera.
Paul Pogba, Marcus Rashford and Zlatan Ibrahimovic all retain their places, despite pre-match suggestions that Mourinho may rest key players.
Manchester United: Romero; Fosu-Mensah, Bailly, Smalling, Rojo; Fellaini, Pogba; Lingard, Mata, Rashford; Ibrahimovic.
Substitutes: Johnstone, Carrick, Schneiderlin, Young, Martial, Depay, Rooney.
Zorya Luhansk: Shevchenko; Sivakov, Chayovskiy, Kamenyuka, Petriak, Rafael, Karavaev, Ljubenovic, Grechyshkin, Sobol.
Substitutes: Chuvayev, Sukhotskiy, Gordiyenko, Lipartia, Paulinho, Opanasenko, Checher.Reuse content