Below-par Manchester United fell to a first league defeat of the season as bottom-of-the-table Wolves proved that relegation is not a formality for them.
United led after three minutes as Nani drilled home inside the near post after turning George Elokobi inside-out.
But Elokobi headed in well soon after with United's defence sleeping as Matt Jarvis executed a short-corner routine.
Kevin Doyle then glanced in just before the break, after which the visitors failed to carve out any clear chances.
Not only will Wolves' hopes of avoiding relegation soar with a fine win that puts them only two points behind 17th-placed Wigan with a game in hand, but United's Premier League title rivals will be seriously buoyed now that their daunting 29-match unbeaten run is over.
Manager Sir Alex Ferguson looked livid with his United team as they failed to usurp the record of his 1999 Treble winners with a display that deteriorated rapidly after Nani's early opener.
Though Wolves remain bottom by virtue of an inferior goal difference to Birmingham and West Ham, they have now beaten five of the top seven - United, Manchester City, Chelsea, Liverpool and Sunderland - this season.
United appeared to pay the price for the absence of in-form England captain Rio Ferdinand, whose calf injury suffered in the warm-up meant Jonny Evans was pressed into action.
Instant drama ensued as Wolves appealed for a penalty as Brazilian right-back Rafael swept away danger from Matt Jarvis with his upper body after 40 seconds.
But United took the lead soon after as Nani showcased the superior side to his inconsistent game.
Breaking into the right side of Wolves' penalty area, he played with Elokobi over and over while ignoring both Berbatov and Rooney as they lurked in the centre with arms aloft.
In a flash of movement he then sent Elokobi the wrong way before cutting inside to power a ruthless left foot shot past Hennessey at the Welshman's near post.
The visitors could have added an instant second, but Rooney screwed an ugly attempt high into Hennessey's arms after Berbatov cleverly found the unmarked England striker.
Yet United may have paid the price for overconfidence as they completely lost their concentration after 10 minutes to let Wolves back in.
As Jarvis took a quick corner Rafael jogged into his penalty area with his back to the ball with United utterly disorganised.
And when it was quickly returned to Jarvis, with United failing to mark up properly, his clean cross was met with a full-blooded header by former Colchester defender Elokobi - who had to stretch his neck back to add power - with Edwin Van der Sar well beaten at full stretch.
Rooney then just failed to find Berbatov as the strong wind took his searching long pass out of his strike partner's stride.
Berbatov, who has scored 13 goals in his past nine Premier League appearances, then brilliantly found space in box with series of effective flicks but his weak shot caused Hennessey no trouble.
But, after Nani went close with a 28th-minute free kick, Wolves dug deep into their resources to turn the tide as they began to control the rest of the half.
Impressive debutant Jamie O'Hara, on loan from Tottenham, nearly squeezed the ball home at the near post but alert 40-year-old goalkeeper Van der Sar improvised to kick the ball away for a corner.
Nemad Milijas almost put Wolves ahead when his 37th-minute free-kick from 20 yards nearly crept inside stranded Van der Sar's far post, but the wicked deflection off Vidic's head took it just wide.
But his free kick three minutes later, from wide on the right, proved a crucial assist.
Wolves team-mates Kevin Doyle and Elokobi both battled to get a headed touch as the ball flew into the net, although Doyle insisted his was the last as they celebrated in front of the joyous home fans at Molineux.
United did have a chance just before the break but, with Ferguson fuming on the sidelines, Nani headed Rafael's right-wing cross over the bar.
Midfield veteran Paul Scholes replaced ineffective Michael Carrick for the second half.
But, for once, his enduring class failed to instigate a real sense of urgency for United although he did come close to connecting with an early low cross.
Wolves, however, looked just as likely to extend their lead as United wasted the ball when well-placed in advanced areas.
Jarvis was a constant threat, and jinked well inside Rafael in the penalty area to work a smart pull-back for O'Hara.
But the midfielder needed more power behind his side-footer as Vidic cleared the danger.
Rafael then needed medical attention as he suffered an alarming-looking dislocated finger, although he was able to continue after it was reset.
Chris Smalling came on for injured Evans, before Mexican forward Javier Hernandez replaced Berbatov.
But Hernandez - United's late saviour on many occasions this season - could not work his magic as a substitute once more.
After O'Hara was replaced by Kevin Foley, seemingly to protect him from receiving a second yellow card, Nani then showed the more frustrating side of his character as he shot wildly into the crowd with a host of team-mates well placed.
And United's desperation became clear when Scholes was booked for handling - rather than heading - a late attempt to steer a cross past Hennessey, although the keeper made sure of the save anyway as Wolves sealed the three points despite five minutes of added time.
The United players were understandably dejected at full-time