Relegation-threatened Wigan shone early on but Edwin van der Sar stood solid.
Javier Hernandez cleverly clipped in rampant Nani’s cross after 17 minutes as the visitors gradually took control.
Mexican striker Hernandez slotted a cool second 15 minutes from time before a Wayne Rooney tap-in and substitute Fabio’s simple shot added a late gloss.
Sir Alex Ferguson’s team came into the match off the back of a disjointed goalless draw at Marseille, but added attacking cohesion to their characteristic defensive stubbornness against a Wigan team who did test them until the killer second goal from Hernandez.
And the confident display sets them up well for Tuesday’s trip to Chelsea, with United now 15 points clear of the reigning champions.
Though Wigan sit second from bottom, they are not cut adrift from mid-table teams and can be hugely encouraged by their showing.
In the low Lancashire sunshine, they had United on the back foot immediately to force a succession of early corners.
The first clear opening came when Vidic uncharacteristically gave the ball away, but his recovery tackle on Charles N’Zogbia on the edge of his own area was perfect.
Going past men with ease, Nani showed first for a United team who had Hernandez partnering Rooney as regular first-choice forward Dimitar Berbatov sat on the bench.
A frustrated-looking Rooney elicited boos after charging into James McCarthy off the ball with what looked like a forearm.
Van der Sar soon came to sloppy United’s rescue after a woeful Paul Scholes error.
Victor Moses pounced on the loose ball but, one-on-one, he could only steer his shot into the broad shoulders of the 40-year-old Dutchman.
But the first bit of real class from United, in the 17th minute, gave them the lead against the run of play.
Rooney made a lung-busting burst past Nani to exchange passes on the left wing with the erratic-but-gifted Portuguese winger.
He quickly whipped a fine low cross along the box which Hernandez – exhibiting his instinctive movement – moved towards before expertly slipping the ball round Ali Al Habsi into his near post.
Wigan did not fold and soon tested Van der Sar once more as he was forced into an outstanding point-blank save from McCarthy, who had been set up by Hugo Rodallega’s skilful flick.
United came within millimetres of extending their lead on the half-hour when Darren Fletcher played a smart pass inside for Rooney, who did the same for Nani.
The winger – clearly comfortable with both feet – cracked a 15-yard left-foot shot past Al Habsi, but it cannoned back off the left upright.
With Scholes a continually classy presence and Vidic blocking shots and clearing crosses like a man possessed, United just managed to keep control of a feisty match.
But Steve Gohouri and McCarthy continued to link well on the right in the second half, while Van der Sar’s hands were stung yet again just after half-time as Maynor Figueroa’s fine long-range shot forced a decent high stop.
Nani soon slalomed into the box, riding tackles, but his shot was saved relatively comfortably.
With United pushing for a second to give them some breathing space, Hernandez fashioned a superb pull-back which Nani and Fletcher came close to connecting with.
Moses then did the same as Hernandez for Wigan – but Rodallega fired his snapshot well over the bar under pressure from United centre-back Chris Smalling, who again ensured that the absence of Rio Ferdinand was not noticed.
Ubiquitous Nani unleashed another shot which was spilled by Al Habsi, who then saved from Fletcher after Rooney had recycled the rebound.
United were rewarded for their growing pressure in the 75th minute when Hernandez, who is proving prolific in his first season in English football, flicked a high ball on for Rooney.
The England striker, still not fully back to his best form, gave a simple return ball as Hernandez nipped through Wigan’s slumbering backline to slot a clinical low finish past Al Hasbi.
Ten minutes later Darron Gibson’s long pass out of defence freed substitute Berbatov, and he unselfishly squared the ball across for Rooney to side-foot into an open net.
At the death, with Wigan well beaten, Fletcher’s deep floated cross was controlled at the far post by Fabio as the Brazilian full-back clipped it inside the near post with his only contribution to the match.
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Premier League: Wigan 0 – 4 Man Utd