There was no Mark Duffy for the Blades, as manager Chris Wilder opted to start with strikers Billy Sharp, Leon Clarke and David McGoldrick.
Wigan had the first chance, Nick Powell's header no problem for goalkeeper Dean Henderson.
The keeper had to be alert to keep out Gary Roberts's free-kick, before Chey Dunkley headed over.
But United took the lead on 24 minutes, Dunkley netting an owl goal after fine work down the flank by Chris Basham.
But the visitors were level on 39 minutes. Nathan Byrne's cross picked out substitute Kai Naismith at the back post, and he hammered in the equaliser.
United edged back in front just before half-time, when Sharp pounced from close range.
And it could have been 3-1, as McGoldrick broke clear one-on-one with goalkeeper Christian Walton, but Antonee Robinson recovered to block the shot.
Clarke got on the end of Kieron Freeman's cross, early in the second half, but Walton did well to tip it wide.