An impressive second-half showing gave Barnsley all three points at Kingsmeadow to leave AFC Wimbledon further in the relegation mire.
The visitors took the lead through Cauley Woodrow’s neat finish from a corner in the 19th minute before Joe Pigott equalised from an Andy Barcham free-kick (36).
The Dons’ then should have had the lead at the interval when Jake Jervis missed a tap-in from close-range before Barnsley stepped up a gear in the second period.
First Kieffer Moore made it 2-1 with a towering header (51) before turning provider for Mamadou Thiam’s thunderous 65th minute strike.
And with the game sewn-up, Cameron McGeehan added some late gloss with the Tykes’ fourth of the afternoon.
The result means AFC Wimbledon are now five league games without a win, bottom of the League One table and seven points from safety.