The match, QPR caretaker boss Chris Ramsey???s first in charge of the club, had appeared destined for a draw until Saido Mane???s injury-time strike.
And despite Ramsey???s side having a goal disallowed with the very last kick of the game, QPR remain firmly in the relegation zone after this rare home loss, while Southampton maintain their push for Champions League football.
Southampton dominated the opening 45 minutes, with midfielder Mane in particular proving a thorn in the QPR???s side.
The lively Senegal international had more than one opportunity to break the deadlock, however, on more than one occasion he was unable to generate enough power in his shot to trouble Robert Green in the QPR goal.
And when the visitors did manage to beat Green, the woodwork denied them, as happened 10 minutes before the break when centre-back Jose Fonte???s close-range volley from James Ward-Prowse???s left-wing corner smacked against the QPR bar.
There were other openings too for the Saints, and none better than after just five minutes when their new winger Eljero Elia found himself one on one with the onrushing Green, only for the Dutchman to panic and fire horribly wide of the gaping goal.
The first half had seven minutes of injury time added on after a nasty looking head injury to Southampton left-back Matt Targett following a clash of heads with QPR???s Matt Phillips, with the 19-year-old stretchered off in a neck brace and immediately taken to hospital.
Ward-Prowse had the visitors??? final effort of the extended first period, only for the England U21 international???s curling free kick from the edge of the area to narrowly miss the target.
However, after the break the contest turned into a war of attrition, with Ramsey attempting to alter the one-way traffic heading his team???s way by introducing recent loan signing from West Ham United Mauro Zarate after 63 minutes.
And that switch appeared to breathe new life into the home side, with top-scorer Charlie Austin ??? in front of watching England manager Roy Hodgson ??? coming desperately close to finally breaking the deadlock 17 minutes from time, only for Fraser Forster to pull off a stunning reflex save to deny the striker.
But then in injury time man-of-the-match Mane got wrong side of the backtracking Nedum Onuoha after a neat flick-on by Graziano Pelle, and after turning his man the midfielder made no mistake with a close-range finish high into the roof of Green???s net.
There was still incredibly time for more late drama, with referee Roger East correctly ruling out Onuoha???s equaliser for a clear foul by the midfielder on Forster.