The Premier League champions have handed a first start to Wilfried Zaha after his arrival from Crystal Palace, while Wayne Rooney is not in the squad due to a shoulder injury
Zaha has impressed during pre-season and is set to make his competitve debut for the Premier League champions, following a £10 million transfer from Crystal Palace in January.
The 20-year-old, who spent the second half of last season in the Championship, scored his first goal for the club in a 2-2 draw with Cerezo Osaka in July.
The rest of the United side shows seven changes from the team which drew 5-5 with West Brom in the last game of the Sir Alex Ferguson era.
Rafael da Silva, who is available despite currently serving a three-match suspension, is at full-back, while goalkeeper David de Gea and Tom Cleverley both start after Rio Ferdinand's testimonial less than 48 hours ago.
As expected, Wayne Rooney is not in the United squad due to a shoulder injury and wingers Ashley Young and Nani are out with knocks.
Meanwhile, Wigan have made one change from the side which hammered Barnsley 4-0 in their Championship opener last week.
James McClean comes straight into the team after arriving from Sunderland on Thursday, while Owen Coyle has also recruited Grant Holt from Norwich this summer and the striker starts up front.
Ben Watson is in the starting line up after coming on as a second half substitute to score the winning goal against Manchester City in the FA Cup final at Wembley in May.
Wigan Athletic: Carson, Boyce, Barnett, Perch, Crainey, Watson, McArthur, McCarthy, McClean, Holt, Maloney.
Subs: Nicholls, Gomez, Espinoza, McCann, McManaman, Fortune, Dicko
Manchester United: De Gea; Rafael, Vidic, Jones, Evra; Giggs, Carrick, Cleverley, Zaha; Van Persie, Welbeck
Subs: Lindegaard, Evans, Anderson, Smalling, Valencia, Kagawa, Januzaj