Steve Cook fired the Cherries ahead with an acrobatic volley in the first half, before Benik Afobe then headed in Matt Ritchie's free-kick on the 79th minute to secure all three points.
The Cherries started brightly at Vitality Stadium and almost took the lead after just two minutes, as Ritchie's rifled effort forced Fraser Forster to parry behind early on.
The visitors were, however, quick to respond. Cedric Soares surged down the right flank and squared for Charlie Austin in the area, but the former Poole Town striker fired wide from close range.
It was AFC Bournemouth that took the lead on the 31st minute, though. Relentless running from Joshua King won a free-kick on the right of the area which Ritchie stepped up to deliver.
The Scotland international's flat cross was then palmed away by Forster in the Southampton goal, but Cook adjusted superbly to acrobatically volley the rebound home.
At this point the Cherries looked a real threat. Max Gradel was sent running down the left and cut dangerously inside, but was unable to keep his strike down.
With 15 minutes of the second half remaining the visitors made their first change of the evening, as Maya Yoshida made way for Steven Davis.
Fourth official Kevin Friend then suffered an injury on the cusp of half time, forcing a delay to the restart as he was replaced by Dean Treleaven.
Once under way, the visitors looked determined to turn around their first half deficit. However a number of crosses towards Austin were dealt with well by Simon Francis and King and Gradel still appeared threatening on the counter.
There was a blow for the visitors shortly after the restart, however, as Austin pulled up and had to replaced by Graziano Pelle.
AFC Bournemouth were then forced into a change of their own as Dan Gosling was introduced in place of the injured Harry Arter.
The substitutions kept on coming and just three minutes later King and Shane Long made way for Lewis Grabban and Dusan Tadic respectively.
The changes for both sides did little to help what had become a patchy second half, though Pelle did drag a 25-yard effort wide of Boruc's post shortly after his introduction.
As Vitality Stadium began to brace itself for a nervy final ten minutes, the second breakthrough eventually came.
A free-kick from deep was delivered in superbly from Ritchie before Afobe nipped in front of Forster and headed past the Southampton goalkeeper to double the Cherries' tally.
With just five minutes remaining Eddie Howe made his final switch of the evening, replacing Gradel with Marc Pugh.
Despite their lead the Cherries continued to push in the closing stages, before Mike Dean's final whistle eventually confirmed another hugely valuable three Barclays Premier League points.
Boruc, Francis, Cook, Surman, Arter (Gosling, 66), Gradel (Pugh, 84), Daniels, Smith, King (Grabban, 69), Afobe, Ritchie
Subs not used: Federici, Elphick, Distin, Murray
Southampton XI: Forster, Soares, Yoshida (Davis, 34), Fonte, Long (Tadic, 69), Mane, Romeu, Ward-Prowse, Van Dijk, Bertrand, Austin (Pelle, 60)
Subs not used: Stekelenburg, Clasie, Martina, Targett
Goals: Cook, 31, Afobe, 79.
Referee: Mike Dean
Attendance: 11,033 (1,347)