On a freezing afternoon at Deepdale watched by 12,153, it looked like honours were going to be shared.
Preston left-winger Ross Wallace had an early effort saved and Barnsley's ex-Preston striker Jon Macken had a shot saved after eight minutes.
Preston striker Neil Mellor had a shot saved and Wallace had a 20-yard curling free-kick also saved by Barnsley keeper Heinz Muller.
In the 21st minute, Dennis Souza lost the ball on the left-hand side to Mellor and he squared the ball low and hard for the assist to Richard Chaplow, who scored his third goal of the season from 12 yards.
Barnsley equalised in the 33rd minute when Jamal Campbell-Ryce ran through with no-one closing him down and he hit a 20-yard low shot into the bottom corner from 20 yards.
In the second half, Callum Davidson and Chaplow had efforts saved.
Campbell-Ryce had an angled shot that was tipped on to the post by the Preston keeper after 51 minutes.
Mellor had two shots saved and Chris Sedgwick had a cross-shot saved.
Substitute Martin Devaney put over a left-wing cross and Macken at the far post brought a good saved out of Andy Lonergan.
With two minutes to go, Preston got the all-important winning goal when St Ledger picked up the ball around the halfway line and ran forward before letting fly from 25 yards.
There was a deflection and the helpless keeper was left wrong-footed and the ball went high into the middle of the goal to make it 2-1 to Preston with captain Paul McKenna having the assist.