Wanderers produced their best performance of the campaign so far to see off Cardiff City at Adams Park in the final game of 2020.
Ryan Tafazolli, making his first appearance since September, crashed home a header from former Bluebirds left-back Joe Jacobson's corner, and David Wheeler doubled the lead with an excellent header from Garath McCleary's inviting cross.
City pulled one back in stoppage time when Junior Hoilett nodded home from close range but the Chairboys stood firm to secure their first victory since early November, building confidence ahead of the visit of Middlesbrough to Adams Park on Saturday.
The freshness rubbed off on the team, who started brightly and saw Mehmeti's shot blocked after excellent work from Ikpeazu and McCleary, while at the other end, Ryan Allsop produced a low save to deny Harry Wilson's shot from the edge of the box.
The breakthrough came from Jacobson's pinpoint corner, which was met by Tafazolli with a towering header past Alex Smithies, while Wheeler then struck a post from close range - though the flag was already up for offside.
After the interval, Sheyi Ojo stung the palms of Allsop and Wilson blazed over as Cardiff threatened, but Wycombe roared back and after Horgan's shot was blocked and Ikpeazu curled wide, the lead was doubled courtesy of McCleary's sumptuous cross which was converted impeccably by the head of Wheeler.
The introduction of Josh Murphy and Junior Hoilett from the Cardiff bench sparked the visitors into life and Wilson saw a back-post header blocked, but the hosts looked comfortable going into stoppage-time with their two-goal lead intact.
Alex Samuel almost made it 3-0 but shot straight at the keeper, and Hoilett's header in the final minute reduced the deficit but there was no time to complete the comeback as Wycombe celebrated their triumph.