Manchester United's attacking trio of Carlos Tevez, Cristiano Ronaldo and Wayne Rooney put their side top of the table for the first time this season.
Tevez (c) scored his second league goal for Man Utd
Initially United were stymied by Wigan but Tevez's darting run and then his strength and composure to drill into the net gave them a second-half lead.
Soon after Ronaldo headed in from close range following a United corner.
United confirmed their dominance when Rooney set up Ronaldo, before the England striker headed in the fourth.
Wigan rarely tested Tomasz Kuszczak, though the United keeper did well to palm away a Luis Antonio Valencia shot after Ronaldo's first goal.
So three more points for United, though this was a win that came at a cost, with Louis Saha pulling out of the game through injury after hurting himself in the pre-match warm-up.
United suffered two more injuries in the first half when Nemanja Vidic and John O'Shea had to go off, two substitutions that disrupted the champions' impressive early rhythm.
But the disruption proved only temporary and two goals in the space of four minutes early in the second half ended Wigan's resistance at Old Trafford.
The champions should have been ahead long before Sir Alex Ferguson was forced to reshuffle his side.
Wigan goalkeeper Chris Kirkland had to react quickly to palm away Salomon Olembe's attempted clearance following a Tevez cross as United began their seige of the visitors' goal.
Ronaldo gathered up the loose ball and looked to be clearly fouled by Michael Brown, but referee Mike Riley waved play on.
Towards the end of the first half United recaptured their early momentum, Ronaldo forcing a save from Kirkland, while Tevez wrong-footed Mario Melchiot before curling the ball over the bar.
United began the second half in ominous mood with Ryan Giggs striking the crossbar with a well-executed half-volley.
We speeded the game up in the second half, the flow of the game was much better. It's coming together
Tevez's goal provided ample demonstration why Ferguson was so keen to bring the Argentine to Old Trafford.
The former West Ham forward had the speed and strength to hold off Kevin Kilbane, before drilling a shot into the corner of the net.
Four minutes later Ronaldo headed in from close range after a United corner and the Portuguese forward capped a fine performance with a cool finish after he had been set up by Rooney.
The England international completed the scoring with a header after Danny Simpson had crossed from the right.
Wigan deployed a five-man midfield and Marcus Bent as a lone striker, a formation that rarely tested United's rejigged defence.
Josip Skoko went close with a shot, while Patrice Evra reacted quickly to hook the ball away from Paul Scharner as the Austrian prepared to shoot.
During the second half Jason Koumas's left-footed shoot went narrowly wide, before Kuszczak saved from Valencia.
Manchester United manager Sir Alex Ferguson on his team's ability to cope with the Vidic/O'Shea injuries:
"Considering all the things that happened I think we've done fantastically well.
"I was very pleased with the football in the second half.
"We had 10 players missing but great credit to the players who played today.
"We speeded the game up in the second half, the flow of the game was much better. It's coming together."
Wigan manager Chris Hutchings:
"We had a game plan which worked well in the first half.
"But as as soon as they scored the first goal they upped the tempo and they could have scored a couple more.
"It's always difficult but while it's 1-0 you have always got a chance. I'm disappointed that we lost our shape."
Man Utd: Kuszczak, Pique, Ferdinand, Vidic (Anderson 21), Evra, Ronaldo, O'Shea (Simpson 30), Scholes, Giggs, Rooney, Tevez (Nani 81).
Subs Not Used: Heaton, Eagles.
Goals: Tevez 54, Ronaldo 59, 76, Rooney 82.
Wigan: Kirkland, Melchiot (Hall 50), Boyce, Bramble, Kilbane, Scharner, Brown, Skoko, Koumas, Olembe (Valencia 66), Bent.
Subs Not Used: Pollitt, Landzaat, Aghahowa.
Ref: Mike Riley (Yorkshire).