Sadio Mane’s injury time goal condemned QPR to their fourth consecutive defeat.
The Senegal international spun away from Nedum Onuoha in the penalty area before shooting across goal into the top corner beyond the dive of Rob Green.
It was a heartbreaking strike for QPR’s caretaker manager Chris Ramsey who was placed in charge following Harry Redknapp’s departure on Tuesday.
Adel Taarabt, Armand Traore and Matt Phillips all started for the Rs having not featured in the 3-1 defeat at Stoke City.
On five minutes Italian international Graziano Pelle got a shot off from distance after nice build up play but Green comfortably saved.
Two minutes later Rangers were given another scare when Green rushed out of his box but Eljero Elia’s first time effort sailed wide of the target.
Southampton continued to take the game to the home side and former Celtic man Victor Wanyama fired wide from just outside the box after Hill headed clear a free kick from Ward-Prowse.
Ronald Koeman was then forced into a change when Southampton left-back Matt Targett was stretchered off after he came off worse in an aerial battle with Rs winger Matt Phillips.
Romanian centre half Florin Gardos was sent on to play alongside Jose Fonte at the heart of the visitors defence with Maya Yoshida switching to left back.
On 25 minutes the impressive Sadio Mane came in off the right wing and let fly from 30-yards but his left footed shot was easily saved by Green. At the other end good defending from Nathaniel Clyne prevented Armand Traore from getting a chance on goal as QPR looked to force an opening goal.
On the half hour mark, Phillips fired wide after bringing down a header from Steven Caulker on the edge of the penalty area.
The visitors were inches away from taking the lead through Pelle, but his shot from six-yards hit the crossbar rather than the back of the net.
Seven minutes were added on at the end of the first half due to the injury sustained by Targett and Elia should have done better when he was in on goal but could only shoot straight at Green with Nedum Onuoha on his tail.
Richard Dunne was lucky to escape a booking when he kicked Elia in the groin area when he went down under a challenge. From the resulting free kick, Ward-Prowse failed to trouble Green as the teams went in level at the break.
QPR’s caretaker manager Chris Ramsey opted against making any changes at half time and from a delightful Phillips cross, Traore headed into the side netting.
With both teams looking to make the breakthrough, Southampton replaced Wanyama with Morgan Schneiderlin and QPR sent on Mauro Zarate for Taarabt.
Both sides struggled to create clear cut chances but on 73 minutes Fraser Forster pulled off a point blank save to prevent Charlie Austin giving QPR the lead, after the striker deflected a shot from Joey Barton which the former Celtic keeper tipped over.
Traore was replaced by Mauricio Isla and Phillips switched to the left wing.
Koeman made his econd substitution replacing Elia with Dusan Tadic.
Injury forced off Dunne and Eduardo Vargas was sent on in his place.
With five minutes remaining a mazy dribble from Zarate ended with him letting fly from 30-yards but his shot sailed just over the bar.
In injury time Mane struck to stun Loftus Road into silence adding to the pressure for the R’s when they travel to Sunderland on Tuesday night.
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