Wayne Rooney got the ball rolling with a clipped finish from Rafael da Silva’s cross, before Michael Carrick swept in.
Rafael bagged a third before half-time with a left-footed shot and Dimitar Berbatov tapped in after the break.
Antonio Valencia rounded off a terrific display with a fine chipped fifth and, in truth, it could have been more as relegation candidates Wigan crumbled.
Defeat leaves the Latics only a point off the drop zone and their recent run of one win in nine matches has left Roberto Martinez’s side nervously looking over their shoulder at the bottom three.
A woeful night out was made all the worse by an injury to keeper Chris Kirkland that meant he had to be withdrawn at half time.
United have won all 10 previous matches against Wigan, and the visitors’ performance bore all the hallmarks of a side resigned to defeat before they had even kicked off.
It was barely a month ago that Wigan went down 9-1 at Tottenham – and if it were not for good fortune they might have suffered a similar fate at Old Trafford.
The Latics failed to put pressure on the ball, allowing the home midfield the freedom of the pitch, and with Rooney dropping deep to cause problems at every given opportunity United were able to create goalscoring opportunities at will.
But, as bad as the visitors were, the hosts were good.
Darren Fletcher patrolled the midfield with purpose, Carrick picked passes for fun, Valencia was a constant nuisance down the right-hand side, while Rooney’s performance will cause the Wigan defence nightmares for months.
United could have been two or three to the good before Rooney broke the deadlock on 28 minutes.
Dimitar Berbatov had claims for a penalty turned down after going down under Titus Bramble’s challenge, Rooney forced Chris Kirkland to tip round the post from 25 yards, Nemanja Vidic had an effort cleared off the line by Paul Sharner, and Rooney – again – curled onto the far post after dancing round Maynor Figueroa on the byline.
Rooney opened the scoring with the deftest of final touches, clipping in Rafael’s cross from six yards out.
Carrick doubled that lead minutes later when he swept home Valencia’s cut-back, and Rafael made it three before half-time when his left-foot shot from the edge of the squeezed home to give him his first goal at Old Trafford.
The second half was always going to be a case of damage limitation for Wigan – but they fell well short of that.
Berbatov ensured little momentum was lost when he poked home the fourth five minutes after the restart after more good work from Valencia, and the Bulgarian very nearly laid on a fifth soon after when his cross was headed against the bar by Rooney.
Despite being almost totally outplayed, Wigan did occasionally string a move together that ensured the United defence was not completely redundant, and Charles N’Zogbia missed a great chance to reduce the deficit when Won-Hee Cho’s pass set him free in the box only for the winger to drift his shot wide, while Hugo Rodallega headed straight at Tomasz Kuszczak from six yards out.
However, they were only brief forays into the opposition half and former Latic Valencia soon added United’s fifth of the night, running on to Rooney’s slide-rule pass to chip over substitute keeper Mike Pollitt and into the far corner.
There was still time for Anderson to drill over and Pollitt to save well when Emmerson Boyce almost deflected a sixth into his own net, but United happily settled for a second 5-0 defeat of Wigan this season – a win that takes their goal difference to +27, two less than Chelsea.