But the late strike condemned Orient to their fourth home defeat of the season and only goal difference keeps them out of the bottom four.
The home side dominated the first half in terms of possession but failed to create too many clear-cut chances.
Even so, Blackpool striker Andy Morrell was in the right place at the right time as he twice cleared goalbound efforts off the line.
First he denied Justin Miller's 20-yard drive after the visitors had half cleared a corner. Then the Blackpool player denied striker Gary Alexander when his header had beaten keeper Rhys Evans.
But Blackpool looked threatening on the break and the visitors went close after just ten minutes when Adrian Forbes sliced through the home defence and sent a shot just wide of the mark.
But it was Orient who quickly took a grip and Shaun Barker almost turned a cross into his own net before Alexander had a shot blocked.
After the break Orient continued to dictate and Shane Tudor raced clear but opted to shoot when Alexander was well placed.
As the game progressed Blackpool threatened to catch Orient on the break and on 70 minutes Morrell sent a header against the bar following a cross from Forbes.
Orient replied with a header from Adam Chambers that drifted wide of the mark, while at the other end Ian Evatt had two good chances for the visitors but saw his first effort blocked and then blasted another attempt over the bar.
But with the game heading towards a draw, Southern struck the vital goal five minutes from time.
Substitute Keigan Parker crossed from the right and, when Alton Thelwell failed to clear, the ball fell to the Blackpool midfielder to rifle home.