The Serbian centre-back has recovered from knee surgery but does not start at Old Trafford as Chris Smalling partners Rio Ferdinand in defence against the Black Cats
The centre-back has not featured for the Red Devils since September 19 when he injured a knee in the Champions League win over Galatasaray which subsequently required surgery.
While Vidic begins on the bench, Chris Smalling partners Rio Ferdinand in defence with Jonny Evans out injured, while Phil Jones replaces Rafael at right-back in the only other change to the side that beat Manchester City last time out.
Sunderland, meanwhile, head to Old Trafford on the back of a morale-boosting 3-0 win over Reading in midweek. Manager Martin O'Neill makes just one change from that side with Danny Rose dropping out and Titus Bramble coming in.
Manchester United: De Gea, Jones, Smalling, Ferdinand, Evra, Valencia, Carrick, Cleverley, Young, Rooney, van Persie.
Subs: Lindegaard, Giggs, Chicharito, Vidic, Welbeck, Scholes, Fletcher
Sunderland: Mignolet, Larsson, Gardner, Colback, O'Shea, Bramble, Johnson, McClean, Cuellar, Fletcher, Sessegnon.
Subs: Wickham, McFadden, Kilgallon, Vaughan, Westwood, Saha.