The visitors scored three times in the second half - Cameron McGeehan squeezing in a low shot, Cauley Woodrow slotting into the bottom corner and Jordan Green tapping into an empty net to stretch the Tykes’ unbeaten league run to 15 matches.
Jacob Brown was given a straight red card for a knee-high tackle on Sam Mantom before the break, just hours after winning the EFL’s Young Player of the Month for January.
But Barnsley were good value for their win, with Alex Mowatt and Mamadou Thiam also sending efforts just off target, as the hosts struggled to create clear-cut chances.
Teenage substitute Charlie Kelman came close to equalising in the second half but failed to bring the ball under control just a couple of yards out and Barnsley goalkeeper Adam Davies clawed it away.
Daniel Stendel’s side, who are bidding to return to the Championship at the first time of asking, have not lost in the league since 8 December and are five points clear of third-placed Sunderland.
The Black Cats have two games in hand in what now looks to be a three-horse automatic promotion race along with Luton following Portsmouth’s demise in form.
For an out-of-sorts Southend it was a seventh game without a win and 18th loss of the season - only bottom two Bradford and AFC Wimbledon have more defeats.
Despite being 13th in the table, Chris Powell’s Shrimpers are just seven points above the relegation zone and have played at least a game more than many other sides around them.