Wise left himself on the bench until late on, when David Livermore was dismissed for two book able offences with the Lions leading through a Neil Harris penalty and a Paul Ifill strike.
But he left his side clinging on desperately for only their second win in six with just nine men when referee Rob Styles showed him a straight red card for a late tackle on fellow substitute Chris Armstrong.
Wise has ruled himself out of taking the job on past his four-week stint, but it was his changes which ultimately made the difference despite the obligatory rash of red cards at the end from Styles.
Robbie Ryan was recalled for the first time in six matches just days after McGhee had told the full-back he could leave the club, and Millwall reverted to the more familiar system McGhee had abandoned for the 1-0 home defeat to Preston which cost him his job.
They carved out the first chance after just four minutes, Harris springing a disorganized offside trap to feed Bob Peeters, who could only deflect the ball wide at full stretch.
Blades defender Mike Whitlow then put a free header over the crossbar at the other end, but Harris struck a stinging left-foot volley on 21 minutes which flew inches wide of the visitors' far post with goalkeeper Paul Gerrard beaten.
Wise spent the first half standing by his dug-out barking orders with his arms folded, and decided to take his place next to Lions chairman Theo Paphitis in the directors box at the start of the second.
Within seven minutes he watched his side take the lead. Abou Fofana sprinted past Rob Kozluk into the penalty area, where the Blades defender hauled him down, and Harris made no mistake from the penalty spot, beating Gerrard low to the keeper's right.
Gerrard then pulled off a stunning diving save from Peeters, who connected perfectly with a header from Fofana's free-kick, but he was at fault from the resulting corner when Ifill doubled the home side's lead.
The winger's first shot cannoned back off a defender straight to him, but his second squirmed underneath Gerrard in the 66th minute to bring his own total to four league strikes this term.
There were nervous moments when Livermore was dismissed with eight minutes remaining for his second bookable offence, and the standing ovation Wise received after bringing himself on for a late cameo turned to disbelief when Styles sent him off, but Millwall clung on grimly through four minutes of added time.