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 debut
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.