Daniel Stendel’s side dominated the first half and led through George Moncur’s first-time volley but Blackpool turned the game on its head in the second half.
The hosts scored two goals in six minutes after the restart with Michael Nottingham finishing off a corner before Harry Pritchard curled an effort into the top right corner from the left.
French striker Armand Gnanduillet then confirmed the victory with a fierce free-kick with 10 minutes to spare.
Blackpool could have been on the scoreboard but John O’Sullivan effort rolled wide.
But it was the Tykes who struck first with Moncur directing a volley into the back of the net from a high Dimitri Cavare cross.
Daniel Pinillos then delivered a low cross with Victor Adeboyejo firing over the bar.
However, Blackpool took the lead with two goals in 10 minutes.
Nottingham got the final touch from a scramble in the box following a corner before Pritchard curled in a top-class strike from the left with 56 minutes gone.
Gnanduillet powered his free-kick over the wall and through the hands of keeper Jack Walton to confirm Blackpool’s victory.
Blackpool: Howard, Nottingham, Daniels (Bola, 81), Tilt, Anderton, Spearing, Thompson, O’Sullivan, Pritchard (O’Connor, 71), Cullen (Delfouneso, 61), Gnanduillet. Unused substitutes: Sims, Turton , Sinclair-Smith, Dodoo.
Barnsley: Walton, Cavare, Jackson, Pinnock, Pinillos, McGeehan (Mowatt, 81), Dougall (Potts, 68), Isgrove (Thiam, 63), Moncur, Bradshaw, Adeboyejo. Unused substitutes: Davies, Lindsay,, J. Williams, B.Williams
Referee: M Heywood.