Stern John's fifth goal of the season settled things at St Mary's as Blackpool came away from the South Coast unlucky not to have secured at least a point.
Simon Grayson was left seething at referee Ian Williamson after the Berkshire official had denied Blackpool midfielder Gary Taylor-Fletcher an equaliser in controversial circumstances.
Just seconds before the ball crossed the line, the referee blew his whistle to haul play back for a Blackpool free-kick for an earlier foul on Danny Coid.
The decision was harsh on Blackpool who spent much of the second period camped in Southampton's half only to receive no help from the match officials.
In a turgid opening 45 minutes, John livened up the proceedings as he collected Bradley Wright-Phillips's pass to turn neatly onto his right foot and plant his finish past Paul Rachubka.
Just minutes before the Trinidad striker's opener, Blackpool had been unfortunate not to take the lead as Andrew Davies' lunge diverted Bartosz Slusarski's pass into the path of Andy Morrell who bent his shot around Kelvin Davis, but it struck the face of the post and was cleared.
The second 45 minutes then bore witness to a real ding-dong affair as both sides piled forward for what would be a crucial second goal of the game.
It was Southampton who nearly put matters beyond Blackpool as Jason Euell was tripped inside the penalty area, but the former Middlesbrough man then saw his spot-kick saved by Rachubka.
Nervy Southampton, without a League win in four, then seemed to retreat into a shell as first Taylor-Fletcher went close before David Fox tested Kelvin Davis from long range.
As the clock ticked down, Taylor-Fletcher was then cruelly denied what would have been a richly-deserved equaliser but further frustration was to come as leading scorer Morrell spurned a golden opportunity.
The former Coventry striker collected Keith Southern's clever chip over the top but, as the Southampton defence raised their arms in hope of an offside call, Morrell instead clumsily spooned his effort well over the crossbar.