Bouncing back from the disappointment of having a fine header chalked off at Fulham, Jose did well to steer home Adama Traore's cross after the break.
His first goal in gold and black, coming in his 13th appearance, was enough to settle a fairly underwhelming affair at Molineux.
Nuno Espirito Santo's side are now on 41 points, with six Premier League games left to play.
Defeat for the Blades, though, sealed their relegation to the Championship.
Not a thriller by any means, but this is a victory which should give Wolves more room to experiment in the final weeks of 2020/21.
Looking at the positives, it is successive wins for Nuno's pack and Jose's barren run has come to an end.
Credit to the 29-year-old as he found the net in style. It was an instinctive finish and should lift a big weight off his shoulders.
Nelson Semedo also played a key role in the goal, coming up with a brilliant block before Wolves – something we have not seen from them in a good while – made the visitors pay with a rapid, clinical counter-attack.
Games on the whole, unfortunately, remain pretty tough to watch.
The first half, in particular, was drab and creativity very much remains an issue for Wolves.
But now they are in no danger of being dragged into a relegation fight, there is scope for Nuno to try some things out.
Players like Vitinha and Morgan Gibbs-White will hope to gain more minutes. Perhaps even youngsters Lewis Richards and Theo Corbeanu – both on the bench for this one – could be handed their senior debuts.
Of course, there is still an onus on picking up results and finishing as high in the table as possible. But fans wouldn't mind seeing them, within reason, throw a little more caution to the wind over the next month.
Wolves made two changes to the side which started the dramatic 1-0 win at Fulham – both of them enforced.
Pedro Neto, having had knee surgery in the week, and Ruben Neves, who is self-isolating after testing positive for Covid-19, were those to drop out.
Joao Moutinho and Willy Boly – back from quarantine – came in while Nuno went for three centre-halves.
United, meanwhile, lined up in their trademark 3-5-2 despite caretaker boss Paul Heckingbottom teasing a switch in system ahead of the clash.
The game started at a slow pace, with Wolves having a bit more attacking intent about them. Jose released Traore – looking to build on his winner at Craven Cottage – but the Spaniard was denied by a well-timed, sliding block from Enda Stevens.
Jose soon had the opportunity to play another through-ball to Traore. He was guilty of trying to be too clever, though, as his reverse pass intended for Daniel Podence – much to Nuno's frustration on the touchline – was intercepted without difficulty.
Wolves, while not putting together free-flowing moves, continued to fashion a few half-chances. A clever back-heel from Boly had to be cleared off the line by Oliver Norwood.
Podence then flashed one over with his laces from the edge of the box, before Rayan Ait-Nouri placed a shot straight at Aaron Ramsdale with his weaker right foot.
Still, a step up in tempo was desperately required as there was a very end-of-season feel in the air. Like a friendly.
United were not doing a lot with the ball and not pressing with great vigour either. And Wolves were unable to shift through the gears as a forgettable first half drew to a close.
Nuno's lot seemed guilty of paying the Blades too much respect, but the Portuguese stuck to his guns for the beginning of the second period.
Semedo tried to make something happen as he sent over a low cross from the byline. Ramsdale, though, was there to collect with relative ease at his near post.
On the other side, Ait-Nouri was slipped through by Jose, but there was nobody in the box to meet the young Frenchman's curling cross.
Wolves, at long last, broke the deadlock right on the hour mark.
United could have taken the lead as Rhian Brewster's ball to the far post found Stevens. However, Semedo vitally got in the way of his effort and a swift counter-attack saw Traore's delivery calmly tucked away by Jose. Drought over.
Coming as a big relief for the Real Sociedad loanee, the goal sparked United into some life.
Stevens soon forced Rui Patricio into a sharp reaction save while the visitors introduced Lys Mousset and Oli Burke.
But it was Wolves – bringing on Vitinha and Fabio Silva – who should have added to their advantage towards the end.
Romain Saiss was denied from point-blank range by Ramsdale, the unbalanced Silva put one straight at the keeper, and then Traore blazed another attempt high and wide.
As it turned out, thankfully, one goal was enough to make it back-to-back victories and condemn the Blades to the drop.
Wolves (3-4-3): Patricio; Boly, Coady (c), Saiss; Semedo, Dendoncker, Moutinho, Ait-Nouri; Traore, Jose (Silva, 77), Podence (Vitinha, 72)
Subs not used: Ruddy (gk), Hoever, Richards, Kilman, Otasowie, Gibbs-White, Corbeanu
Goal: Jose (60)
Sheffield United (3-5-2): Ramsdale; Ampadu, Egan (c), Bryan; Baldock, Osborn (Mousset, 75), Norwood, Fleck, Stevens; McGoldrick, Brewster (Burke, 75)
Subs not used: Foderingham (gk), Jagielka, Bogle, Lowe, Brunt, Gordon, Lundstram
Referee: Robert Jones (Merseyside)