In a bid to secure back-to-back wins for the first time since early November, Gareth Ainsworth stuck with the same starting line-up that were victorious at Adams Park just four days prior to Barnsley's visit.
Valerian Ismael opted to make three changes to the side that was successful on the south coast at the weekend, bringing in Daryl Dike, Callum Styles and Michael Sollbauer in the places of Conor Chaplin, Jordan Williams and Toby Sibbick.
The high-flying visitors opened the scoring on the stroke of half time, when Cauley Woodrow netted from the penalty spot to claim his 11th goal of this Championship campaign.
In the 49th minute, Dike doubled Barnsley's lead, when he nodded in from close-range.
20 minutes from time, Wycombe were handed a lifeline when Alex Mowatt saw red after a challenge on Scott Kashket, but Barnsley's American loanee netted his second of the game to ensure the three points were taken back to Oakwell.
Story of the match
In an opening ten minutes where both sides were unable to carve out any clear-cut opportunities, Barnsley deployed a more direct game-plan, and played off the physicality of Daryl Dike.
The hosts also demonstrated their intent to win from the get-go and used Uche Ikpeazu's aerial presence to progress up the pitch.
The Tykes, who have been brimming in confidence in recent weeks, were confined to a succession of set -pieces in the early exchanges, but the hosts defended resolutely and looked assured in their defensive third.
The first opportunity of the game fell to Dominik Frieser in the 19th minute, who saw his driven effort denied by David Stockdale's feet in the Wycombe goal.
Three minutes later, the Austrian winger was presented with another opportunity to give his Barnsley side the lead, but he fired his left-footed effort over Stockdale's bar, after he had capitalised on a defensive mix-up.
As the half wore on, Barnsley started to insert their dominance, utilising their wing-backs in attacking positions and restricted the Chairboys to a couple of breakaway opportunities
In a half where set-pieces became increasingly influential, Barnsley centre-back Michal Helik was next to threaten, but his deflected effort flashed narrowly past Stockdale's near post.
In the 45th minute, Cauley Woodrow converted from the penalty spot after Ryan Tafazolli was adjudged to have brought down Helik - a decision that was highly-disputed by the home side, with the referee Darren Bond sticking to his original discussion after conferring with his linesman.
Four minutes into the second half and it was two. Dike anticipated Mads Anderson's cushioned header to beat Stockdale to the loose ball and head into an empty net.
In a bid to change the dynamic of the game, Wycombe brought on Scott Kashket for the lively Anis Mehmeti in a like-for-like swap.
In typical Ismael fashion, the Tykes made a triple substitution on the hour mark, bringing on Carlton Morris, Toby Sibbick and Aapo Halme for Frieser, Sollbauer and Palmer.
Wycombe continued their attempts to break the Tykes' high defensive line, but a combination of the offside flag and the sweeping nature of Barnsley goalkeeper Bradley Collins, kept out the bottom club's attack.
In the 74th minute, Mowatt was shown a straight red card after a perceived dangerous tackle on Kashket.
Defying the man, Dike grabbed his second of the game, when he tapped in from Callum Brittain's inch-perfect cross from the right wing.
In the 85th minute, Ikpeazu tapped home a late consolation but Barnsley held on for yet another victory.
The Tykes won their ninth game in their last ten outings with victory in Buckinghamshire. Once again their high-pressing football helped them earn victory on a night where it was difficult to play their usual attack-minded football.
The Chairboys' push for survival is all but over. Games are running out and there is still a sizeable gap between Wycombe and Birmingham City, who are the current occupiers of the all-important 21st position.
Daryl Dike netted his fourth and fifth goals in his eighth game for the Yorkshire club. His pace and power caused Wycombe's defence problems throughout the entirety of the 90 minutes, and he showed a clinical side to his play when the opportunities arose.