Wanderers came away empty-handed from their first visit to Barnsley in 15 years, in a game of three goals, two penalties and a red card for Adam El-Abd.
Cauley Woodrow scored twice for the hosts, firstly from the spot after a foul by Luke Bolton, and then from Jacob Brown's assist after the visitors lost Bolton to injury after a lengthy delay for treatment.
El-Abd was sent off in stoppage time following an altercation under provocation with Cameron McGeehan, before Joe Jacobson netted a consolation from 12 yards after Scott Kashket was tripped.
Gareth Ainsworth made three changes to the side that lost 3-0 at Luton seven days earlier, bringing a more youthful look to the attack with Alex Samuel, Luke Bolton and Nick Freeman replacing Nathan Tyson, Matt Bloomfield and Adebayo Akinfenwa.
Wanderers enjoyed an assured start, mostly down the right-hand side with former Tyke Jason McCarthy linking up neatly with Bolton, with the latter winning an early corner that nearly curled straight in, only for the home keeper Adam Davies to make a goal-line intervention.
Then the pair combined again, taking advantage of a lethargic start from the Tykes’ backline, to lay on a chance for Freeman, but his effort from 12 yards following Bolton’s cut-back was blocked to safety.
Daniel Pinillos saw a shot deflect wide with the hosts’ first effort on 11 minutes, but after Wanderers failed to clear, Mike Bahre fell as he and Bolton contested the ball in the area and referee Matthew Donohue pointed to the spot, giving Cauley Woodrow the opportunity to break the deadlock as he rolled it into the corner from 12 yards.
It came as a hammer blow for the Blues after more than matching their second-placed hosts from kick-off, but Barnsley gradually began to find their rhythm, almost doubling their lead when Dani Pinillos let fly from distance and his deflected shot needed a superb save from Ryan Allsop to prevent it from nestling in the top corner.
Jacob Brown drew a comfortable save from Allsop from 20 yards, before Freeman was presented with a golden chance to level, meeting McCarthy’s low cross with a first-time shot which was kept out by the legs of Davies.
Then Wanderers were indebted to Allsop for a vital save just before the break, rushing out to block Alex Mowatt’s chance with his legs as the midfielder met Woodrow’s clever through-ball inside the area.
It remained 1-0 at the interval, but the Blues battled well at the start of the second period, with Alex Samuel having the ball whipped away from under his nose as he prepared to turn it home from close range.
Then Luke Bolton sidefooted straight at Davies after a clever corner routine resulted in the ball being laid into his path, with the home fans beginning to grow restless as their side’s lack of ball retention.
But then came a moment of real concern when Bolton went down motionless after contesting the ball by the corner flag, seemingly caught by an innocent arm in the challenge, and requiring lengthy treatment on the pitch. Eventually he was able to walk off, aided by the medical staff, with Nathan Tyson taking his place.
After the restart, Allsop parried away Cameron McGeehan’s long-range drive, before the hosts swapped Mamadou Thiam with Ryan Hedges.
And the stoppage for the injury had come just at the right time for Barnsley, who were able to regroup and come back stronger after being on the back foot, doubling their lead all too simply when a through-ball carved open the backline and Jacob Brown crossed low for Woodrow to crash the ball into the roof of the net.
Wycombe needed a change, and it came – a double one in fact – with Adebayo Akinfenwa and Scott Kashket replacing Freeman and Cowan-Hall.
McGeehan flashed a shot wide from 25 yards and Brown headed wide as the visitors found themselves on the wrong end of some questionable decisions from the first-year EFL referee, while Woodrow was denied a hat-trick on 78 minutes by another Allsop save, before Liam Lindsay headed the corner over the bar.
Tyson was booked for an alleged foul on Dimitri Cavare, and Jombati followed soon after for a more certain foul on Woodrow, before Barnsley brought off Mike Bahre as Victor Adeboyejo took his place.
Wanderers could have had a goal back when Tyson lashed an effort too close to Davies from Akinfenwa’s flick, and then the Tykes made their final change with Alex Mowatt departing and Kenny Dougall coming on.
There were 10 added minutes due to the stoppage for Bolton’s injury, in which Jason McCarthy was booked for a crunching tackle which was dwarfed in comparison by McGeehan’s moments later, also earning a yellow. But then as McGeehan confronted Gape by going face-to-face with the midfielder, he was restrained by Adam El-Abd who then saw a straight red card after the referee took advice from the fourth official.
Jacobson was booked for a foul moments later before referee Donohue spotted a trip on Kashket in the area, enabling Jacobson to score from the spot deep into stoppage time.
But there was no time for the Blues to find a second, ultimately leaving Oakwell defeated after a curious battle with plenty of talking points, but won by the in-form Reds.