The Belgian international, who could cost United in the region of £90million, scored three goals in pre-season before bagging another in the Super Cup defeat to Real Madrid.
Jose Mourinho has never lost an opening Premier League game as a manager - winning seven and drawing one - while United have not lost at home to West Ham in the last ten years.
Nemanja Matic, another summer capture, is also expected to start but Mourinho has a host of injury absentees, with Luke Shaw, Ashley Young and Marcos Rojo all on the sidelines.
The Hammers are likely to hand a debut to Javier Hernandez - the 29-year-old could face his former club for whom he scored 37 goals in a five-year spell.
On loan goalkeeper Joe Hart will start in goal but Bilic still has a long injury list to contend with, as Michail Antonio, Andy Carroll, Manuel Lanzini, Cheikhou Kouyate and Diafra Sakh are all missing.
The two sides met three times last season- twice in the league and once in the League Cup - with United winning two of those games, although this fixture ended in a 1-1 draw.