The Latics went ahead through an own goal from David Vaughan, before the visitors levelled with a Craig Gardner penalty.
Steven Fletcher then sent Sunderland on their way to maximum points, his superb one-two making it six goals in seven appearances against the Latics for the Scot.
Fletcher's first owed much to his lightning reactions after Ali Al Habsi had turned away his header, with the second an instinctive curling strike from Adam Johnson's lay-off.
New-boy Angelo Henriquez scored a late consolation for Wigan, nodding home Shaun Maloney's far-post cross 11 minutes from time.
"Fletcher was fantastic," said O'Neill. "It was not just his goals but also his whole centre forward play. We took great heart from his performance."
"We've had to show a lot of fight and determination. Wigan threw a lot at us and were never out of it.
"It was all hands to the pump at the end and I am delighted with the result."