The Tykes put the impending departure of leading scorer Vaz Te to West Ham behind them and produced a first-half display which swept previously in-form Derby aside.
Matt Done opened the scoring after a fine move, then an Andy Gray penalty and Scott Wiseman's first goal for the Yorkshire club stunned the Rams.
Nigel Clough's side were a different side in the second half and dominated possession but although Jamie Ward pulled a goal back with a fine free-kick and Tom Carroll scored a late debut goal, the damage had already been done.
The visitors had conceded just one goal in their previous five Championship games but they were made to pay for some sloppy first-half defending.
The Tykes had Derby on the back foot from the off and it needed a magnificent reflex save from Frank Fielding to keep out Jim McNulty's header from an inviting Michael Tonge corner nine minutes in.
But Keith Hill's side were in front just a minute later when a slick four-man move resulted in Done beating Fielding with a measured finish.
The Rams were not at the races and they were two behind after just 21 minutes, when Gray blasted a penalty straight down the middle to give Fielding no chance after Done had been tugged back by John Brayford.
And it came as no surprise when the home side added a third goal after 29 minutes, when more neat passing cut open the Derby defence and full-back Wiseman produced a tidy finish to open his account for the Tykes.
Tonge, who also spent a spell on loan with Derby, was enjoying an impressive debut and the midfielder called Fielding into action once again as the former Blackburn keeper palmed the ball away.
The travelling Derby fans voiced their displeasure at the half-time whistle and Rams boss Clough clearly had a few choice words to say to his side at the break, as his side looked far more lively after the resumption.
Ward had a chance to reduce the deficit but the diminutive forward's attempted lob was easily caught by Luke Steele.
Ward gave Derby a lifeline after 68 minutes when he rifled home a free-kick from 25 yards which appeared to go through the wall.
Barnsley were struggling to get out of their own half as Derby bossed the midfield and Ward fired another strike just over the crossbar.
Derby debutant Carroll had a big shout for a penalty but referee Andy Woolmer waved play on and although the on-loan Tottenham midfielder pulled another goal back deep into stoppage-time, the Tykes held on for all three points.