An improved second-half display from the Wanderers ultimately counted for nothing as defensive frailties proved costly in a 2-1 defeat to Accrington Stanley.
On a heavy pitch, neither side were able to carve open many goalscoring opportunities in the first half but the visitors went in front when Joe Jacobson slotted home from an unmarked position following a corner.
The hosts were more inventive after the break and soon pulled level when Scott Rendell finished smartly from Gareth Ainsworth's through-ball.
But another set-piece brought about the winner as Charlie Barnett's free-kick was directed into the top corner by Phil Edwards with eight minutes remaining, and Stanley held on for the points.
Gary Waddock responded to Tuesday night's defeat at Southend United by making three changes - one of which was enforced due to Matt Bloomfield's injury - with Jon-Paul Pittman and Anthony Straker making way for Gareth Ainsworth, Ben Strevens and Danny Foster.
A deluge of rain overnight resulted in a muddy pitch which made playing conditions difficult, and as such, goalscoring chances were few and far between for either side. Accrington seemed to be content to put men behind the ball and frustrate the hosts, but Wycombe battled well to their credit and created a handful of openings.
Scott Rendell saw an effort disallowed for a shirt pull following Scott Donnelly's free-kick while Donnelly himself and Ben Strevens both missed the target with a shot from distance and a header respectively.
The pacy combination of Marvin McCoy and Gareth Ainsworth in particular seemed to the Blues' best attacking outlet and they continuously sprinted past the left-back to deliver a cross, but the sticky conditions in the box often made life hard for strikers to keep their balance and get their shot away.
Jimmy Ryan twice saw curling efforts miss the target from distance as Accrington enjoyed rare forays into Wycombe territory but, for the most part, they maintained their defensive mentality, much to the detriment of the football match as a spectacle.
So it came as a hammer blow to the Blues when they fell behind two minutes before half-time, courtesy of the first shot on target of the entire game. Accrington worked a corner short and it was laid off to Joe Jacobson 15 yards out, who picked his spot and found the back of the net through a crowd of players.
Stuart Beavon then flashed a header wide as the hosts looked for a response, but the Blues ultimately finished the half one goal down and in need of a boost to turn the game - and their faltering form - back into their favour.
It almost came within seconds of the restart when Scott Rendell flicked Scott Donnelly's free-kick towards the top corner, but the ball whistled just past the post, acting as a reminder of the attacking strength that the Wanderers possess.
And Accrington didn't heed the warning as they again left Rendell in space, and this time he made no mistake in levelling the scores with a cool finish into the corner. Gareth Ainsworth's clipped through-ball was missed by Sean Hessey and Rendell capitalised, taking a good first touch before converting past Alex Cisak.
The visitors almost hit back immediately when Luke Joyce saw Nikki Bull divert his drilled shot over the crossbar after the midfielder's initial drive was blocked, before Marvin McCoy cleared off the goal-line from a Stanley player's goalbound effort which resulted from the corner.
All of a sudden the game was in full swing, and a smart move involving Gareth Ainsworth and Stuart Beavon gave Rendell the chance to complete the turnaround on 57 minutes. The ball was worked to the striker six yards out but, with his back to goal, he could only spin and fire narrowly wide with a defender in close attention.
Terry Gornell shot wide of the near post from 25 yards before Gary Waddock made his first change of the game, replacing Stuart Beavon with Jon-Paul Pittman.
The striker's impact was almost immediate as he just failed to connect with Rendell's header towards the back post, but as Wycombe pushed forward in numbers, there were often spaces for Stanley to attack on the break and Terry Gornell should have done better with a free header on 69 minutes, before Pittman shot straight at the keeper at the other end.
Accrington, to their credit, were far more inventive than in the first half and regained the lead with seven minutes when a free-kick from Charlie Barnett was nodded home by Phil Edwards. It was another lack of marking which had cost the Blues and Nikki Bull had to be alert moments later to prevent a third when Terry Gornell found space in the box.
That spelled the end of the chances for either side as Stanley dug deep to thwart the Blues' late quest for an equaliser, with Alex Cisak holding on to Dave Winfield's near-post header in stoppage time.
Wycombe must now pick themselves up for the visit of Burton Albion to Adams Park on Tuesday ahead of the trip to Macclesfield next weekend.