If there is the ultimate nightmare scenario for Wigan, it is a fixture against United.
The Red Devils have won all 10 of their Premier League fixtures against Wigan, scoring 31 goals and conceding only four.
For good measure, United also beat Wigan 4-0 in the 2006 Carling Cup Final.
United could have been 3-0 up before Wayne Rooney broke the deadlock in the 28th minute.
In two amazing minutes almost midway through the first half, Nemanja Vidic had a shot cleared off the line by Paul Scharner, Rooney hit the inside of a post and Dimitar Berbatov missed a golden opportunity when through one-on-one with goalkeeper Chris Kirkland.
When Wigan were finally cracked, there was no way back for Roberto Martinez's side.
Antonio Valencia, who joined United from Wigan for £17million in the summer, found Rafael de Silva rampaging down the right.
The Brazilian crossed to the near post and Rooney got in before Titus Bramble to hook his shot into the net from six yards.
United doubled their lead four minutes later. Berbatov fed Valencia on the right and he turned the ball back into the centre of the penalty area for Michael Carrick to score with a well-placed low right-foot shot from 15 yards.
United made it 3-0 in the last minute of the first half. Darren Fletcher picked out Rafael on the edge of the Wigan box and he evaded two challenges before scoring with a left-foot shot.
Wigan were 4-0 behind five minutes after the interval. Valencia, who was a constant thorn in the side of his former club, crossed from the right edge of the box and Berbatov stabbed in a right-foot shot from 10 yards.
Rooney hit the bar with a header form close range soon after and it was fitting that Valencia should complete the scoring in the 75th minute.
Rooney's slide-rule pass found the Ecuadorian racing into the box and he scored with a clever chip from 12 yards.
Tomasz Kuszczak made two fine saves to deny Hugo Rodellega, but when it comes to United versus Wigan games there is only ever one winner.