Three goals in a blistering six-minute spell midway through the first half sent rampant Wigan back to the top of the Championship table and increased the problems for beleaguered Blades boss Neil Warnock.
Warnock saw his side suffer their third consecutive defeat as the Latics' feared strikeforce of Nathan Ellington and Jason Roberts took advantage of slack marking to leave the United manager facing a highly-interesting interval team-talk.
Ellington struck after 28 minutes when he latched on to a poor clearance from Phil Jagielka to volley past United keeper Paddy Kenny from just inside the area.
Four minutes later Roberts added the second from eight yards after Nicky Eaden and Gary Teale had combined down the right.
When Teale found Roberts, he converted the simplest of chances.
Still the Latics weren't finished and two minutes later Ellington scored the goal of the game when he picked up Per Frandsen's throughball and held off the challenge of Jagielka before curling the ball around Kenny from just inside the area.
United had little to offer in reply except an over-robust approach that saw a first minute booking for striker Jack Lester for aiming a kick at Wigan keeper John Filan.
Lester was fortunate that referee Nigel Miller was in a lenient mood as the card should have been red.
A further booking followed for defender Chris Morgan as United relied on muscle rather than skill but they posed a rare threat when Filan saved well from Ashley Ward.
Warnock made a double substitution at the break, handing striker Tommy Black his debut while bustling frontman Jonathan Forte replaced the injured Lester.
It made little difference as the home side continued to force the pace and they might have added a fourth goal midway through the half only for Lee McCulloch to see his header saved by Kenny.
The home side weren't to be denied however and in the dying minutes Roberts added his second when he rounded keeper Kenny following a delightful pass from Wigan substitute Alan Mahon.
MAN OF THE MATCH: Nicky Eaden (Wigan) - He produced an excellent display in both defence and attack on his first appearance of the season.