Both wingers are nursing injuries and so will not be involved for the season-opening showpiece.
United will also be without unsettled striker Rooney, who remains sidelined by a shoulder injury.
The 27-year-old, who has been selected in England's squad for the friendly with Scotland next week, has yet to feature for the Premier League champions in pre-season as question marks remain over his future with the club.
Robin van Persie, Nemanja Vidic and Patrice Evra are all expected to return to the side after United were beaten 3-1 in a friendly by Sevilla on Friday.
Wilfried Zaha is also likely to feature after joining the club in the summer from Crystal Palace.
"[We will] take just about everyone that's fit. We are one or two short, likes of Nani, Ashley, Wayne are not available for the game at Wembley," said David Moyes, who has overseen an inconsistent first pre-season as United boss.
"Apart from that nearly all others players, if everything goes well, are fit and available to travel.
"It's a really important fixture because it's the start of the season for us."
Wigan will continue to be without club captain Gary Caldwell who had a hip operation in the summer.
They will also have to cope without fellow defender Ivan Ramis who is still recovering from a knee ligament injury picked up at the end of last season.
However, winger James McClean is likely to make his debut for the club after joining from Sunderland this week.
A host of summer signings are also likely to feature for the Latics, including defender Leon Barnett, midfielder James Perch and striker Grant Holt.
Championship side Wigan began their domestic season with an emphatic 4-0 at Barnsley.