Oxford United's poor run continued as they were undone by a moment of real quality from Joel Grant.
The forward danced past two tackles and buried a low shot into the net for the only goal of the game.
It inflicted a fourth defeat in five games for United, who were again unable to make the most of their chances.
Jon-Paul Pittman hit the post in the first half, while Alfie Potter spurned the best chance after the break.
Wycombe had chances to wrap up the game late on, but they held on to claim all three points.
United made three changes to the XI which started the 3-2 defeat at Aldershot on Easter Monday.
Two were enforced, with Michael Duberry in for the suspended Michael Raynes and Pittman replacing Sean Rigg, who was ruled out with an ankle injury.
The other alteration saw James Constable restored to the side in place of Simon Heslop.
The striker led the line in a changed system, with Pittman, Potter and Tom Craddock playing behind him in a 4-2-3-1 formation.
They were on the front foot early on as the front four found space to pose Wycombe problems.
Constable was the only player to exert Chairboys goalkeeper Matt Ingram, fresh from a loan spell with Oxford City.
His 11th-minute shot was comfortably saved, while Scott Davies and Craddock fired wide with their sights of goal in the opening quarter of an hour.
A hurried clearance from Luke McCormick gave Wycombe their first opening, on 17 minutes.
It fell to Jo Kuffour, whose first-time lob from 40 yards was not powerful enough to cause the keeper problems.
But McCormick could do nothing about Grant's quality finish two minutes later.
The Wycombe forward burst into the box past two challenges and lashed a low shot into the corner to put the visitors in front.
United almost responded immediately, thanks to some good advantage played by referee Graham Salisbury.
Pittman shrugged off a foul out wide to swing in a cross which Craddock headed over from close range.
The winger looked lively on his first start since December and provided United's best moment of the half.
A spell of pressure led to Constable finding Pittman, who turned and flashed in a shot from an angle which beat Ingram but hit the outside of his left-hand post.
Again converting chances was proving United's biggest problem.
Neat work from Damian Batt and Potter saw the former find space in the area, but his cutback was scuffed apologetically wide by an off-balance Andy Whing.
They were not helped by a lack of quality on set pieces, with Davies only finding the first man with both his corners before the break.
Both sides carved out gilt-edged chances early in the second half. Wycombe were the first to threaten, when Jo Kuffour timed his run to perfection, springing the offside trap.
Josh Scowen's flick on sent the striker through on goal, but McCormick got just enough on his shot to keep it out.
At the other end Potter sliced through to face Ingram, but he fluffed the chance with a weak shot straight at the goalkeeper.
Pittman skimmed the crossbar with an overhead kick shortly afterwards as United began to build up a head of steam.
It did not last, though, and United's challenge fizzled out, not helped by losing Constable to injury.
Wycombe twice came close to a second goal, which would have sealed the victory.
Dave Winfield escaped Duberry's attention at a corner but could not keep his header down.
With ten minutes left a loose backpass from Batt played in Scowen.
McCormick did well to anticipate the danger and spared the full back's blushes with a smart block.
Wycombe only had one nervous moment late on. Ingram dropped a long throw in stoppage time which fell on the line, but he gathered before anyone in yellow could bundle the ball into the net.
Oxford Utd: McCormick, Batt, Duberry, Wright, Davis, Whing, Davies, Pittman, Potter, Craddock (Smalley 52), Constable (Parker 73). Unused subs: Crocombe, Heslop, O'Brien, O'Dowda, Long.
Wycombe: Ingram, Harriman, Winfield, Doherty, Dunne, Spring, Lewis, Scowen, Grant, Kuffour, Wood. Unused subs: Harrison, Johnson, Ainsworth, Andrade, McCoy, Kewley-Graham, Morias.
Referee: Graham Salisbury.
Attendance: 6,777 (1,132 visitors).