Antonio Valencia returns to the side after missing the 3-0 win over Sunderland on Sunday.
Michael Carrick comes in for Marouane Fellaini, who captained the Red Devils against the Black Cats.
Mourinho has also opted to replace Ander Herrera with Marcus Rashford.
Manchester United fans set off flare and burn scarf ahead of Anderlecht clash Thu, April 13, 2017
Manchester United fans were in high spirits ahead of their side's Europa League quarter-final clash with Anderlecht at the Constant Vanden Stock Stadium (8.05pm)
Play slideshow TWITTER•FACEBOOK 1 of 7
Manchester United fans have been making themselves heard in Brussels
As expected, Sergio Romero keeps his place in goal.
David De Gea is on the bench along with Luke Shaw, with Matteo Darmian picked at left-back.
There is no place in the squad for Wayne Rooney, who misses the tie through injury.
Anderlecht's Constant Vanden Stock Stadium
Anderlecht: Ruben, Appiah, Mbodji, Nuytinck, Obradovic, Tielemans (c), Dendoncker, Stanciu, Bruno, Kiese Thelin, Acheampong
Subs: Boeckx, Deschacht, Spajic, Chipciu, Capel, Teodorczyk, Hanni
Manchester United: Romero, Valencia, Bailly, Rojo, Darmian, Pogba, Carrick, Mkhitaryan, Lingard, Rashford, Ibrahimovic
Get Quotes on Home Insurance
Subs: De Gea, Blind, Fosu-Mensah, Shaw, Fellaini, Herrera, Martial