Wigan: Shaun Maloney's goal earned Wigan a 1-0 victory over Manchester United that helped cut the champions' lead over Manchester City to five points on Wednesday. (Agencies)
The Latics had a first-half effort by Victor Moses ruled out, with replays showing Gary Caldwell was harshly penalised for a challenge on David de Gea, but Maloney scored the only goal just after half-time.
It was United's first Premier League defeat since the 3-0 loss at Newcastle at the start of January, ending a run that saw them drop just two points in 12 matches.
United have five matches remaining, including a trip to Eastlands to face Manchester City at the end of the month, as they look to close out their 20th title.
Wigan, who have lost just twice in 10 matches, had never managed to get a single point against United in 13 previous league meetings but this victory took them a significant step towards avoiding relegation.
They may have felt that they had wrongly had a goal ruled out but Wigan would have been full value for a half-time lead.
The Latics dominated possession from the start and United were thankful to Michael Carrick for getting back to clear when Maloney's cross looked to have picked out Franco Di Santo in a dangerous position.
A short corner from Maloney saw the ball worked to James McCarthy and the Republic of Ireland international's powerful drive was tipped over the bar by David de Gea.
The Spanish goalkeeper did well to force his way through a crowd to punch away the Maloney corner that followed before Jean Beausejour's follow-up flew well wide of goal.
United were struggling to get a foothold in the game but finally threatened when Carrick threaded a pass through for Ryan Giggs and the veteran midfielder's low effort was deflected wide by Gary Caldwell.
A corner from Giggs was headed wide by a combination for Phil Jones and Wayne Rooney but the visitors were growing increasingly frustrated, with manager Sir Alex Ferguson remonstrating with Rooney for losing the ball in a challenge with McCarthy.
Moses showed some quality to skip past Jonny Evans only to have his shot blocked wide by Rio Ferdinand.
From the Maloney corner that followed, the unmarked Moses thumped a header past De Gea but as the home fans celebrated, referee Phil Dowd blew for a free-kick for Caldwell's challenge on the United goalkeeper.
The home team were furious at the call but were grateful to see a curling shot from Rooney fly wide just before the interval.
Ferguson took off Ashley Young, bringing on Tom Cleverley at half-time, but four minutes after the break, Wigan took the lead in some style.
Maloney took another short corner to Beausejour and after receiving the return pass, he drifted past Antonio Valencia and curled a shot into the top corner.
Rooney bent a shot over from just outside the area as United looked for an immediate response.
But a frustrated Ferguson pulled the England striker off for Nani midway through the second half as he attempted to inject some life into his team's flat performance.
United were angered when Dowd waved away appeals for a penalty after a Phil Jones cross appeared to flick up on to the hand of Maynor Figueroa.
With Jones limping heavily, the visitors, who had already made their three substitutions, were still looking unlikely to pull level and Nani wasted another opportunity when he shot well over from 25 yards.
Moses could have sealed it when he burst past Ferdinand, only to have his shot turned away by De Gea.
The striker also had a shot deflected wide after Ferdinand had pulled off a fine block from Mohamed Diame before Al Habsi denied Danny Welbeck at the other end.
Wigan: Shaun Maloney's goal earned Wigan a 1-0 victory over Manchester United that helped cut the champions' lead over Manchester City to five points on Wednesday.