Blues came unstuck against a rejuvenated Burton Albion in front of the Sky Sports cameras at Adams Park.
The Brewers - managed for the first time by Jimmy Floyd Hasselbaink - opened the scoring with their first real chance when Phil Edwards powered home a header from close range from Matty Palmer's corner.
Palmer was again the architect with an incisive through-ball which allowed Alex MacDonald to convert through the legs of Matt Ingram.
Wycombe were given hope when Hogan Ephraim was tripped in the box and Paul Hayes fired home the resulting penalty, and Ephraim came close to levelling the scores moments later on his home debut.
However, hopes of a comeback were short-lived when Jacob Blyth headed home from Damien McCrory's cross and Wycombe had to finish the game with ten men after Alfie Mawson sustained a nasty head injury after Gareth Ainsworth had made all three subs.