The Japan international is included in the Red Devils' starting XI for the first time this season, while the £27 million Belgian is also handed his full debutShinji Kagawa will make his first starting appearance of the season when Manchester United take on Bayer Leverkusen at Old Trafford.
The Japan international has found first-team opportunities limited after a busy summer on Confederations Cup duty, but takes his place in an attacking United team.
Deadline-day signing Marouane Fellaini has also been handed his full debut, having replaced Wayne Rooney during Saturday's 2-0 home win over Crystal Palace.
In defence, Chris Smalling makes his return at right-back in the absence of the injured Rafael.
Manchester United: De Gea; Smalling, Ferdinand, Vidic, Evra; Carrick, Fellaini, Valencia, Kagawa; Rooney, Van Persie
Subs: Lindegaard, Evans, Fabio, Anderson, Young, Cleverley, Chicharito
Bayer Leverkusen: Leno; Spahic, Boenisch, Omer Toprak, Reinartz; Donati, Rolfes; Sam, Can, Son; Keissling
Subs: Palop, Wollscheid, Bender, Hilbert, Oztunali, Derdiyok, Kruse.