The England defender recently returned to full training after being out with a groin injury, but reports had claimed that he would not have been fully fit to play.
Ferdinand, however, has come into the starting XI to replace Michael Carrick at the back and partner captain Nemanja Vidic at center half.
Carrick will return to his midfield duties in midfield and plays alongside Tom Cleverley, with Paul Scholes and Nick Powell both on the bench.
Also coming into the starting line-up for all come into Manchester United are goalkeeper Anders Lindegaard and forward Danny Welbeck.
Lindegaard comes in for David De Gea, while Welbeck gets the start over Javier Hernandez and will play alongside Robin van Persie in the forward line, with the injured Ashley Young making way.
Nani, Ryan Giggs, and Jonny Evans are all amongst the substitutes.
Southampton vs Manchester United
Southampton: K.Davis; Clyne, Fonte, Hooiveld, Fox; S.Davis Schneiderlin, Ward-Prowse; Puncheon, Lambert, Lallana.
Subs: Rodriguez, Gazzaniga, Lee, Do Prado, Richardson, Mayuke, Seaborne
Manchester United: Lindegaard; Rafael, Ferdinand, Vidic, Evra; Carrick, Cleverley, Kagawa; Valencia, van Persie, Welbeck.
Subs: Evans, De Gea, Giggs, Hernandez, Nani, Scholes, Powell.
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