Wolves' hopes of Premiership survival took a battering as Saints condemned them to their fourth successive defeat.
James Beattie fired the visitors ahead after Jody Craddock lost control.
Claus Lundekvam poked in his first-ever Saints goal from close range, but Henri Camara narrowed the deficit after springing the visitors' offside trap.
Wolves pressed for an equaliser but they left gaps - and Kevin Phillips was twice able to find space to fire home in the dying minutes to seal the win.
It was Southampton's third away win of the season and moved them to ninth in the Premiership.
Paul Sturrock's men looked like having a comfortable afternoon as they forced Wolves keeper Paul Jones to save twice inside the first 10 minutes.
First he cut out a dangerous Phillips cross then, on eight minutes, he parried a venomous shot from the player.
25 mins: Beattie fires Saints ahead
58 mins: Lundekvam increases lead
72 mins: Camara gives Wolves hope
89 mins: Phillips extends lead
90 mins: Phillips seals victory
Camara had Wolves only early chance of note, blasting just wide from 20 yards.
The visitors were dominating play and it was no surprise when they opened the scoring on 25 minutes.
Beattie hit home from 15 yards after a dreadful blunder by Craddock, who lost control of the ball in the danger area.
It could have been worse for Wolves had Phillips showed more composure minutes later when clean through, but the striker blasted his left-foot effort over.
Wolves struggled to get a hold on the game and chances were at a premium.
Alex Rae had the best of the opportunities for the home team, blasting wide from long-range.
Camara and Kenny Miller both headed over for Wolves, but the home side were not troubling Antti Niemi.
Wolves were playing like a side in danger of the drop, and began the second half as sluggishly as they finished the first.
The fans began to get on their back, and the mood did not improve as Lundekvam scored his first Southampton goal in 285 appearances.
Prutton floated in an inch-perfect free-kick, and Lundekvam pounced at the far post to seemingly put the visitors in command.
Yet Wolves, who had threatened little throughout the match, were given a lifeline with 18 minutes to go.
Camara sprung the Saints offside trap and finished coolly past Paul Jones.
But despite late pressure, the home side could not find the breakthrough, and Phillips made them pay at the death.
With Wolves committing men forward, Phillips ran clear and made no mistake from 18 yards.
And to add insult to injury, he did a repeat performance in injury-time to give the scoreline a flattering sheen.
Wolverhampton: Jones, Irwin (Cameron 83), Craddock, Butler, Naylor, Camara, Ince, Rae, Kennedy, Ganea (Cort 45), Miller (Newton 62).
Subs Not Used: Oakes, Luzhny.
Booked: Butler, Camara.
Southampton: Niemi, Telfer, Higginbotham, Lundekvam, Dodd (Hall 53), Fernandes (Anders Svensson 85), Folly, Delap, Prutton, Phillips, Beattie.
Subs Not Used: Smith, Griffit, Ormerod.
Referee: M Halsey (Lancashire).