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Wayne Rooney returned for Manchester United as headed goals from Patrice Evra and Javier Hernandez saw them move level on points with leaders Chelsea.
Evra headed home Park Ji-Sung's cross to break the deadlock before half time after hesitancy from Ali Al Habsi.
Wigan later had Antolin Alcaraz sent off for two bookable offences before Hugo Rodallega was red carded for a wild lunge on United defender Rafael.
Hernandez then sealed the win when he headed in from Rafael's centre.
It was an important victory for the Old Trafford outfit who took advantage of defeats for Premier League leaders Chelsea and second-placed Arsenal as Sir Alex Ferguson's men moved level on points with the champions.
Wigan's record against United had been poor with Roberto Martinez's side losing all 11 of their previous meetings. They were also beaten 5-0 twice by United last season but despite the odds being stacked against them they started brightly at Old Trafford.
In fact, of the clear-cut opportunities, Wigan enjoyed the better of the first-half chances.
First, Jordi Gomez fired over the bar from close range after Nemanja Vidic made a mess of a clearance while Ronnie Stam also struck wide following more, poor United defending.
Soon after Charles N'Zogbia weaved his way past three United defenders before firing straight at Edwin Van der Sar who did well to close the angle at the feet of the Wigan man.
And on the stroke of half time the Latics were denied a penalty after Vidic hauled down N'Zogbia but Wigan's appeals were waved away by referee Martin Atkinson.
At the other end United created very little with their final ball often letting them down. Nani went close with one deflected strike while also forcing Al Habsi into a scrambled save from a curling free kick - but by in large the hosts were poor.
It took until the 45th minute for United to break the deadlock and it came from an unlikely source, with Evra heading home Park's cross from close range for his first goal in the three and a half years.
United waited until the hour before introducing Rooney and his return from a five-week absence was met with cheers and jeers from the Old Trafford faithful, with his bitter contract negotiations that resulted in him belatedly signing a new five-year deal still fresh in the memory.
Soon after, Alcaraz was sent off for a foul on Darren Fletcher as he picked up his second booking of the match as Wigan's task became that much harder.
Wigan's woes continued minutes later as 10 men became nine, with Rodallega red carded for a dangerous two-footed lunge on Rafael.
Sensing an opportunity to increase their lead United sent on Hernandez to partner Rooney up front.
Rooney went close to doubling United's lead but his header from Rafael's cross was tipped over the bar from Al Habsi.
But where Rooney failed, Hernandez succeeded, heading another Rafael cross past the Wigan keeper from close range for his fourth league goal of the season.
Late on, Nani tested Al Habsi with a decent strike from the edge of the area while Hernandez also bundled wide from close range following another fine cross from Rafael.
In the dying moments of the game Rooney scuffed an effort straight at the Wigan keeper while Evra inexplicably fired wide from the angle of the six-yard box as the match ended 2-0.
Credit: BBC
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