Manager Sir Alex Ferguson has also handed starting places to Chris Smalling at right-back and Alexander Buttner at left-back, with Rafael and Patrice Evra both left out of the squad completely.
Rio Ferdinand and Nemanja Vidic, who returns to the starting line-up have been partnered to play at centre-back, while Ryan Giggs also starts for the Barclays Premier League leaders.
Anderson, Danny Welbeck, and Ashley Young have also been handed starting places, with Michael Carrick, Nick Powell, Shinji Kagawa and Javier Hernandez amongst the substitutes.
A win for Manchester United would see them going 15 points clear at the top of the EPL standings, after defending champions and second place Manchester City were beaten 2-0 at Everton in the earlier game.
Meanwhile, Reading make three changes to the side that lost to Aston Villa in the last outing with Jem Karacan, Nicky Shorey and Garath McCleary coming in to start.
Manchester United v Reading Team Starting XI
Manchester United: De Gea; Smalling, Ferdinand, Vidic, Buttner; Welbeck, Giggs, Anderson, Young; Rooney, van Persie.
Subs: Lindegaard, Evans, Valencia, Hernandez, Carrick, Powell, Kagawa.
Reading: Taylor, Shorey, Kelly, Pearce, Mariappa, Karacan, Leigertwood, McAnuff, McCleary, Robson-Kanu, Hunt.
Subs: McCarthy, Gunter, Harte, Morrison, Akpan, Blackman, Le Fondre