Spurs without Luka Modric as youngster Jake Livermore continues to deputise while home side welcome Chicharito back to the bench after several weeks out through concussion
With Rio Ferdinand and Nemanja Vidic both being forced off in last weekend's win at West Brom, Jonny Evans and Phil Jones start in the centre of defence at Old Trafford.
Fellow youngsters Tom Cleverley and Danny Welbeck keep their places after impressing at the Hawthorns, while Javier Hernandez returns to the bench after recovering from the concussions sustained in their pre-season tour of the United States.
American Brad Friedel makes his competitive debut for Spurs, but the away side are without star midfielder Luka Modric who manager Harry Redknapp claimed wasn't focused enough to start, with rumours of a move to Chelsea continuing to circulate.
Having impressed during their midweek thrashing of Hearts, Jake Livermore retains his place in midfield alongside Niko Kranjcar, with Tom Huddlestone on the bench for Redknapp's side.
Manchester United 4-4-2: De Gea, Smalling, Jones, Evans, Evra; Nani, Cleverley, Anderson, Young; Rooney, Welbeck.
Subs: Lindegaard, Berbatov, Giggs, Park, Hernandez, Carrick, Fabio.
Tottenham 4-4-1-1: Friedel; Walker, Dawson, Kaboul, Assou-Ekotto; Lennon, Livermore, Kranjcar, Bale; Van der Vaart; Defoe.
Subs: Gomes, Bassong, Corluka, Huddlestone, Jenas, Townsend, Pavlyuchenko.