The hosts were level going into the break despite numerous chances from Welbeck but the floodgates opened with goals from Scholes, Chicharito, Buttner and Powell.
Chicharito had a fourth minute penalty saved by Ali Al Habsi after he was adjudged to have brought down Danny Welbeck, but a Paul Scholes close-range effort, a goal from the Mexican and debut finishes from Alexander Buttner and Nick Powell, all in the second half, were the difference.
It was a day of landmarks for three of Sir Alex Ferguson's men as Ryan Giggs made a record 600th Premier League appearance, whilst Scholes and Rio Ferdinand played their 700th and 400th match for the club.
Robin van Persie and Shinji Kagawa started on the bench as they were nursing knocks picked up on international duty.
United should have been 1-0 up inside the first five minutes when the on-rushing Welbeck was clipped by Al Habsi in the area. Replays suggested it was a harsh decision and the goalkeeper did well to save Chicharito's weak effort from the spot.
The visitors held their own the first half but it was Welbeck who was proving to be a pain up front for the hosts.
He had four chances in the opening 25 minutes. His first was a volley which just went wide and left Al Habsi stranded, before an effort was blocked by Gary Caldwell.
From the resulting corner, Scholes and Welbeck had further volleys blocked and the England international then headed over from a Carrick center.
Wigan nearly scored with a header of its own with an effort sandwiched in between United's chances. Shaun Maloney whipped in a a free-kick on the right and Ivan Ramis rose highest but failed to keep the ball down.
The second half proved a step too far for Wigan as the floodgates opened.
Scholes finished just inside the six-yard area following a bout of pinball in the box. The visitors just could not get the ball clear and the landmark-celebrating midfielder was on hand to rifle home past Al Habsi on 51 minutes.
Twelve minutes later and it was two. Chicharito atoned for his first-half penalty miss, helping in Buttner's cross from what initially looked like an offside position A second look saw Maynor Figueroa keeping him on.
Buttner deserved a goal for his lung-bursting runs down the left-hand side and eventually, one of those runs finally paid off.
He beat three Wigan defenders for pace before side-stepping Ramis. The ball almost went out of play on the byline but instead of letting it go out, he smashed it across the face of the goal and the ball bounced off Al Habsi and into the goal.
The best of the goals was the fourth and final goal of the game. Welbeck burst into the Wigan half and ended up in a dead-end. The ball should have been cleared but ended up at the feet of Chicharito, who laid off to Powell on the edge of the area. The former Crewe man took a touch before rifling home from 20-yards to seal the victory.