For the Blades it was the third 1-0 win on their travels, with Rob Hulse hitting the winner with his fifth of the season.
But Neil Warnock's side felt they were robbed of a second-half spot-kick while Wigan's Kevin Kilbane blew a great chance to earn at least a share of the points.
Desperate to bounce back after the midweek defeat by Arsenal, Wigan were boosted by the return of skipper Arjan de Zeeuw after a month out with a damaged toe.
But midfielder Paul Scharner - free from suspension - missed out after picking up a knee injury in training.
United, fresh from a 2-2 draw against Aston Villa, had midfielder Michel Tonge back after a seven-week lay-off with an ankle injury. But youngster Stephen Quinn kept his place in the starting line-up after impressive performances in recent games. There was also a welcome return for defender Claude Davis after injury.
It was the first meeting between the sides at the JJB since 2004 when Wigan won the championship fixture 4-0.
Tonge signalled his return early on from a Keith Gillespie corner but the shot, set up by Davis, was blocked and cleared.
United went close when Quinn supplied a pinpoint cross from the left, but Danny Webber's textbook glancing header flew over.
Leading scorer Henri Camara had Wigan's first chance but snatched at the shot from just outside the area, and put it wide.
The Latics could have cashed in when Emile Heskey took advantage of a slip by Quinn out on the right. He got the cross into the danger area, but Lee McCulloch's header lacked both power and direction.
The Blades too were short of punch up front with Hulse heading straight into the arms of the Wigan keeper from Gillespie's cross and Webber fired one wide after the Latics were caught on the break.
Fitz Hall made a timely recovery from a knock to deny Webber an opportunity, clearing the danger with a header back to Chris Kirkland.
But the Blades grabbed the lead in first-half stoppage time. Gillespie's cross floated beyond the back post, it was turned back inside by Quinn and Hulse stuck out a boot to flick it past Kirkland .
The goal stood despite Wigan claims that the United frontman struck from an offside position.
The Latics responded to a half-time pep talk from Paul Jewell and instantly turned up the heat.
Paddy Kenny kept out a real blockbuster from Denny Landzaat before Republic of Ireland star Kilbane squandered a real gift.
Rob Kozluk handed him possession and a clear run on goal but the ex-Everton winger - yet to score since his £2.5million move from Goodison - failed to come up with a finish.
Leighton Baines just missed the target from long range and Lee McCulloch forced a one-handed save from Kenny with a header.
But United were fuming when ref Peter Walton awarded a penalty and then changed his mind after consulting his assistant.
The Blades were insistent that De Zeeuw handled Gillespie's cross, but the replay suggested that it struck his thigh and the ref got it right.
Gillespie, who has had two spells on loan at Wigan, used his speed to race clear, and force Kirkland into action with a terrific shot.
Webber went for the follow-up but the ball hit the post and was cleared.
A rare slip by De Zeeuw almost let Hulse in but Baines saved the day with a covering tackle and at the other end, sub David Wright was wide with a header.
Then deep in injury time, McCulloch saw a header cleared off the line.