Brian McDermott's side had won eight games on the trot before drawing at Doncaster in midweek, but two goals in as many minutes at the start of the second half got them back on the winning trail before their dominance was confirmed with two further efforts.
Jobi McAnuff broke Barnsley's resistance in the 47th minute when he crashed home a low shot from the edge of the penalty area and Karacan lashed home a second, high into the roof of the net, two minutes later.
Barnsley manager Keith Hill said this week he had been "appalled" by his side's recent form and their winless run was extended to six matches when Karacan added a brilliant third goal from 25 yards in the 65th minute, while Jason Roberts neatly converted a fourth in the closing stages.
Barnsley handed a debut to defender Lee Collins, who joined on loan from Port Vale earlier this week, while teenager Danny Rose made his first start for the club and Korey Smith joined him in midfield.
Hayden Mullins made his debut for Reading after joining on loan from Portsmouth on Thursday and winger Jimmy Kebe returned to the visitors' starting line-up.
Reading striker Noel Hunt forced a fine save from Barnsley goalkeeper Luke Steele with an angled shot from inside the penalty area after just 45 seconds and 10 minutes later Rose was a fraction wide with an audacious 30-yard lob in a lively opening.
Steele held a routine catch from Roberts' shot, but pulled off another super save to turn away Mikele Leigertwood's blistering drive as Barnsley held firm until half-time.
The visitors struck twice in as many minutes soon after the restart to break Barnsley's resistance.
Roberts laid the ball off for McAnuff on the edge of the penalty area in the 47th minute and the Reading midfielder arrowed a low shot beyond Steele into the bottom corner.
Barnsley had hardly caught their breath when the visitors doubled their lead two minutes later.
The home defence failed to clear the ball in the penalty area and Karacan pounced to lash it into the roof of the net from 12 yards.
Roberts then pulled his left-footed shot off target when poised to add another from inside the area in the 57th minute, but the Royals were not to be denied a third goal thanks to Karacan's super finish.
Ian Harte supplied the free-kick and striker Hunt this time teed the ball up on the edge of the box and Karacan fired an unstoppable right-footed shot into the top corner.
Hill sent on Stephen Dawson and David Cotterill for Rose and Nathan Doyle, while Smith, Craig Davies and Frank Nouble went close with long-range efforts for Barnsley, but there was to be no consolation for the Yorkshiremen as Roberts converted a fourth goal from Alex Pearce's pass in the 90th minute.
