Wanderers' unbeaten run came to an end as Plymouth secured a deserved 2-0 win at Adams Park.
The damage was done in the first half as Lewis Alessandra thundered the ball home after a counter attack, and Peter Hartley converted from close range from a deep corner to double the lead.
Luke McCormick made a couple of important saves to preserve a clean sheet but in truth the Blues didn't look like rescuing a point on a disappointing evening.
Gareth Ainsworth kept faith with the same side that won 1-0 at Cambridge at the weekend but his usually resolute backline came up against a lively Argyle attack in the opening exchanges and Lewis Alessandra had two chances to break the deadlock, firstly skewing his shot wide of the near post before his drilled effort was cleared by Alfie Mawson.
However, it was a case of third time lucky for the former Morecambe man as he collected a pass on the counter-attack following a poor Wycombe corner, and raced through to power home the opener on 20 minutes.
The hosts looked to find a quick response and Sam Wood volleyed over before Aaron Holloway shot straight at Luke McCormick after Matt Bloomfield laid the ball into his path.
But they were left stunned on 30 minutes when a deep corner was turned goalwards by Peter Hartley as Matt Ingram struggled to break through a crowded six-yard box to meet the ball, having done well to keep out Alessandra’s firm effort just moments earlier.
Wycombe were denied a route back into the game when Sam Wood’s header was tipped over the bar by McCormick before Alessandra again caused a scare at the other end, laying it off to Olly Lee whose low shot struck the base of the post and went wide.
The start of the second half didn’t exactly offer the home fans hope as Argyle came close to adding a third when Lee’s powerful shot from a tight angle cannoned off the underside of the bar and Reuben Reid headed the rebound over the crossbar.
However, Wanderers did come close to halving the deficit when Fred Onyedinma sent a looping header towards the back post but Hogan Ephraim couldn’t turn it goalwards when Luke McCormick doing enough to cause a distraction.
Courtney Senior was handed his professional debut as he replaced Fred Onyedinma and showed some impressive early touches as the Blues began to apply pressure around the Pilgrims’ box, but the goal didn’t come and the visitors were able to hold on relatively for a second successive win.
The Blues will look to return to winning ways when they face Newport County at Adams Park on Saturday.
Attendance: 3,078 (522 from Plymouth)
Winning 50/50 Draw Number: 135186
Prize Money: £483.00