The Dutch striker is set to make his full debut for his new club at home to Fulham, with Michael Carrick reprising his role as a centre-back and Shinji Kagawa keeping his place
It will be the Dutch striker's first appearance at Old Trafford since joining United, and he looks set to be partnered by Shinji Kagawa in attack, with Ashley Young and Antonio Valencia providing support from the wings.
In the centre of the pitch, Tom Cleverley and Anderson start, bringing back a partnership that started last season's Premier League campaign promisingly, but was brought to an end by injuries.
Meanwhile, Michael Carrick reprises his role as centre-back alongside Nemanja Vidic, while Rafael returns at right-back in a shuffle of personnel from Sir Alex Ferguson.
There is the welcome return for United of Jonny Evans on the bench, as Sir Alex names him alongside three strikers, in Rooney, Chicharito and Danny Welbeck, as well as the two veterans of the squad Ryan Giggs and Paul Scholes.
For the visitors, John Arne Riise is replaced at left-back by Matthew Briggs in the only change from their 5-0 victory over Norwich on the opening day of the season.
Moussa Dembele is set to keep his position as a deep-lying central midfielder, with Damien Duff, who retired from international football this week, on the right wing, youngster Alex Kacaniklic on the left, Bryan Ruiz in the centre, and new striker Mladen Petric pitting his wits against Carrick and Vidic up front.
New signing Hugo Rodallega is on the bench for the second week in a row after winning a penalty last week, and he is joined by Steve Sidwell, who converted the effort from 12 yards.
Manchester United XI: De Gea; Rafael, Carrick, Vidic, Evra; Valencia, Cleverley, Anderson, Kagawa, Young; Van Persie.
Subs: Lindegaard, Evans, Rooney, Giggs, Chicharito, Welbeck, Scholes.
Fulham XI: Schwarzer; Riether, Hangeland, Hughes, Briggs; Duff, Diarra, Dembele, Kacaniklic; Ruiz; Petric.
Subs: Stockdale, Kelly, Baird, Sidwell, Kasami, Rodallega, Halliche.