The Reds are beaten away from home in Sky Bet League One as Randell Williams' second half strike for the Chairboys settles a contest that otherwise lacked quality.
The hosts made it a club record six consecutive home victories as they triumphed over the Reds for the first time in history.
In dire conditions, Williams' powerful strike early in the second period was enough to see Wycombe to another three points and consigned Barnsley to another defeat on the road.
With the Reds without the suspended Dimitri Cavaré, Barnsley Head Coach, Daniel Stendel had to bring in Jacob Brown to play right back but it was otherwise the same lineup that knocked out Southend in the FA Cup a week earlier.
It was a rather uneventful first half, if we're being honest. The game was played in a very competitive spirit, there was no inch given by either side, but chances were at a premium.
Alex Mowatt tested debutant 'keeper Stephen Henderson from range, but the on-loan stopper did well to keep him out.
Chairboys' skipper Adam El-Abd saw a header comfortably saved by Reds' skipper Adam Davies.
The home side were very direct and pumped a lot of balls over the top as well as playing over a lot of crosses from deep positions but the Barnsley rearguard dealt with it all, and then came a big controversial point in the match..
Mowatt slipped George Moncur into the box, the Reds' number 10 jinked forward and was seemingly halted unfairly, falling to the ground. But referee Antony Coggins went the way of the hosts, much to Moncur's frustration who was then booked for his reaction to the decision.
Right on half time, the best chance of the half..
A Mowatt corner was met by the rising Ethan Pinnock, the ball looked destined for the top corner but Henderson clawed it away to keep the game scoreless at the break.
HALF TIME: Wycombe 0-0 Barnsley
The Reds looked lethargic upon the second half getting underway and the home side had a 10 minute spell of pressure which eventually proved fruitful.
Not before an outstanding save from Davies; the Welsh international producing a world-class stop to deny Williams, parrying a goalbound strike onto his crossbar.
Barnsley didn't heed the warning however, and on 54 minutes, Wycombe took the lead.
Cauley Woodrow was replaced through injury as the hosts were about to take a corner, Jordan Williams on in his place. That corner was punched clear by Davies, Brown couldn't clear from the edge and Williams tried his luck from 20 yards out, the shot finding the roof of the net despite Davies' best efforts.
Brad Potts was immediately introduced, replacing Mike Bähre as Daniel Stendel looked for a quick reply.
Our hosts were seemingly happy with the one goal and began to retreat and defend for the rest of the half, inviting pressure from Barnsley. And the Reds did indeed improve from then on, but a glaring lack of quality restricted to Stendel's side to half-chances.
Mamadou Thiam came on for Zeki Fryers, with Pinnock becoming an emergency striker and Mowatt going to left back.
Brown saw a header fly a yard or so wide from a Mowatt corner; Moncur saw a rocket of an effort blocked and fall just wide of the post, Moore tried a shot on the turn but his effort lacked power and trickled wide, and then in the last minute of injury time Pinnock hooked over the bar from 12 yards out.
It was a disappointing afternoon for Barnsley ahead of next week's clash with table-topping Portsmouth at Oakwell.
FULL TIME: Wycombe 1-0 Barnsley
Davies, Brown, Pinnock, Lindsay, Fryers (Thiam), Mowatt, McGeehan, Bähre (Potts), Moncur, Woodrow (J.Williams), Moore.
Unused: Greatorex, Jackson, B.Williams, Isgrove.
Att: 5,225 (941 Reds - outstanding support)