Two goals in the opening 10 minutes gave the Latics a surprise 2-0 lead which left the home faithful in stunned silence.
Firstly they countered quickly from an Arsenal corner, with Jordi Gomez finding Franco Di Santo unmarked in the middle and the Italian lifted the ball over Wojciech Szczesny before volleying it side-footed into an empty net.
Ninety second later, Gomez was on hand to add a goal to his earlier assist when he bundled in from close range following great work from Victor Moses down the Wigan left.
Arsenal were further disrupted when Mikel Arteta was forced off injured immediately after Wigan's second, but they responded well to create chances of their own.
The Gunners could have gone into the break on level terms but Tomas Rosicky, who provided Arsenal's first goal, blazed the ball over from Robin van Persie's pullback.
Vermaelen nearly nodded in a second after the break while Andre Santos also struck off target from close range as Arsenal wasted chances to equalise.
The lively Moses could have restored Wigan's two-goal cushion but put his tame shot straight at Szczesny when through one-on-one with Polish stopper.
Arsenal continued to apply pressure but stubborn defending from the visitors saw them hold on and move a step closer to Premier League safety.