On a wet a miserable night in the midlands, the Blades were soundly beaten by the league leaders.
To compound the defeat at Wolves, goalkeeper Simon Moore was sent off following a challenge outside his penalty area.
Holmes started for the first time in the televised fixture, replacing Leonard, who dropped to the bench. Clarke, Stearman and Evans - all ex Wolves - started, as did former Lane loanee Coady for the home side.
Wolves started the brighter and had already gone close with a Costa volley ahead of taking the lead after five minutes. Cavaleiro was involved in the build-up but the 20-yard curler from NEVES was unstoppable, finding the top corner.
In a frantic start, all the Blades could muster was Evans firing over on his return to Wolves.
Another Costa effort was deflected wide but the home side had a second goal on the half hour. Intricate passing in and around the box resulted in JOTA playing a one-two before slotting past Moore.
Cavaleiro went close to a third but he mis-hit his effort ahead of United changing formation, Basham moving into midfield. Before the break, the visitors had a spell of pressure but the only chance of note was Wilson forcing a save out of Ruddy.
The first opportunity of the second half saw the home side's Douglas curl a free-kick into the Blades wall and Holmes, off balance, sliced wide for United following an Evans cross.
Bonatini shot wide after a neat turn and boss Wilder searched for fresh impetus when he introduced Leonard and Donaldson.
However, moments later, the game was taken away from the Blades. From a through ball, Moore raced out of his goal to try and clear but he connected with Jota. With the Wolves striker on the deck, United's goalkeeper was shown a straight red card.
Young goalkeeper Eastwood was introduced for his Blades league debut, Wilson making way, but from the resulting free-kick CAVALEIRO's effort found the bottom corner, with the aid of a deflection off the wall.
With the game effectively over as a contest, Wolves continued to attack. Afobe was off target with a header and Eastwood's presence was enough to put off Bonatini.
There was little for United fans to get excited about late on and after the final whistle boss Wilder admitted his side was well-beaten.
Wolves: Ruddy, Doherty, Douglas, N'Diaye, Bennett, Cavaleiro (Afobe 77), Neves, Boly, Coady, Costa (Bonatini 65), Diogo (Gibbs-White 81).
Unused: Batth, Enobakhare, Hause, Norris.
Blades: Moore, Baldock, Stevens, Fleck, O'Connell, Basham (Leonard 71), Clarke, Wilson (Eastwood 76), Stearman, L Evans, Holmes (Donaldson 71).
Unused: Lundstram, Sharp, Duffy, Lafferty.