Daniel Stindel’s side led through George Moncur’s sensational volley as they controlled the majority of the first half.
But Blackpool took over in the second half with two goals in six minutes. Michael Nottingham pounced for the final touch from a corner before Harry Pritchard curled in a superb strike from the left to put the Seasiders ahead.
As Barnsley deflated in the second-half offering little, Armand Gnanduillet confirmed the result with a forceful free-kick on 80 minutes.
The hosts could have been ahead inside six minutes, though. Mark Cullen and John O’Sullivan linked up for a one-two play, but O’Sullivan’s angled shot trickled wide.
The Reds struck first on a counter-attack to move ahead; Dimitri Cavare sent a high ball in from the left wing for Moncur to volley home first time on 19 minutes.
Blackpool responded after the restart as a scramble in the box from a corner led to a shot rebounding off the underside of the cross-bar before Michael Nottingham poked the ball home.
However, Harry Pritchard bided his time on the left wing before cutting inside and stroking a stunner into the top right corner on 56 minutes.
With 10 minutes to play, Gnanduillet stepped up and powered home a fierce free-kick strike through the hands of despairing keeper Jack Walton.
Blackpool: Howard, Nottingham, Daniels (Bola, 81), Tilt, Anderton, Spearing, Thompson, O’Sullivan, Pritchard (O’Connor, 71), Cullen (Delfouneso, 61), Gnanduillet.
Subs not used: Sims, Turton , Sinclair-Smith, Dodoo.
Barnsley: Walton, Cavare, Jackson, Pinnock, Pinillos, McGeehan (Mowatt, 81), Dougall (Potts, 68), Isgrove (Thiam, 63), Moncur, Bradshaw, Adeboyejo.
Subs not used: Davies, Lindsay,, J. Williams, B.Williams.
Referee: Mark Heywood.
Attendance: 1,937 (990.)