Javier Hernandez returned to the side after a brief rest with a couple of goals and Robin van Persie was also on target twice in a comfortable victory over the struggling Latics.
United thought they had broken the deadlock in the 11th minute when Hernandez broke and fired past Ali Al Habsi, but the Mexico striker was correctly adjudged to be offside.
Wigan took 20 minutes to secure their first clear sight of goal but Jean Beausejour made a real hash of an inviting cross that dropped at his feet and fired high, wide and not very handsome.
Soon after, a van Persie free-kick caused havoc in the box, but Wigan managed to clear after an Al Habsi fumble, and Tom Cleverley had an effort blocked by Ivan Ramis as United upped the tempo.
But the goal they had been threatening came on 35 minutes when Patrice Evra forced Al Habsi into a decent save, after a complete mis-kick on his first attempt, and Hernandez pounced to convert the rebound.
It was 2-0 two minutes before the break with Van Persie on target for the 15th time in the league this season, Hernandez making the most of a bit of fortune to play in the Dutchman, who cut inside Ramis and curled past Al Habsi.
Edgy home fans would have expected a response from their team after half-time, but it proved anything but as they spent long spells camped in their own half, some awful passing giving United the chance to sit on their advantage and play keep-ball.
Despite that, United almost allowed Wigan back into the game just before the hour when Arouna Kone converted a Franco di Santo cross-shot at the back post but, like Hernandez earlier on, he was also flagged for offside - this time far less clear-cut.
Hernandez lobbed just over the bar after Al Habsi had a rush of blood to the head, but it was game over on 63 when Van Persie's free-kick fell to him 12 yards out and he smashed home his second goal of the afternoon.
Chris Smalling might have been a touch lucky to avoid being sent off, not long after coming on as a sub, for pulling down Kone and Jordi Gomez curled the resulting free-kick inches wide.
But United still had time for a fourth goal two minutes from time when Van Persie matched Hernandez's double after horrible defending let sub Danny Welbeck in to set him up for a tap-in that rounded off one of their simpler wins of the season.