Wanderers lost an FA Cup first round tie for the first time in six years, going down 2-0 to fellow League 1 side Luton Town at Kenilworth Road.
The Hatters' excellent home record this season gathered pace when Andrew Shinnie curled home an exquisite opener before the break, and Harry Cornick later capitalised on a mistake by Adam El-Abd to stroke home the second.
Both sides named their strongest possible line-ups though Wanderers had to do without Bryn Morris, who was denied permission to play by his parent club Shrewsbury, while Darius Charles joined an injury list already containing Adebayo Akinfenwa, Matt Bloomfield, Nathan Tyson and Michael Harriman.
Wanderers started well and won a corner which was eventually cleared before Harry Cornick was presented with a golden chance at the other end, latching on to Joe Jacobson’s underhit backpass but seeing his powerful drive beaten behind by Ryan Allsop.
Then James Collins lashed wildly over from distance as a fast start carried all the hallmarks of a classic cup tie, though it settled down with Wycombe collecting a couple of knocks which took the sting out of the game.
Alex Samuel almost nicked the ball away from the keeper and last defender as the two Hatters dithered just outside the box, though James Shea’s slide tackle just about retained possession for the hosts, and then Fred Onyedinma sent a header over the bar from Jason McCarthy’s cross.
Adam El-Abd and Sonny Bradley both headed harmlessly wide from deep corners and then Elliot Lee curled a free-kick harmlessly wide from over 25 yards out, before Jason McCarthy was harshly booked when James Justin went down on the wing during a chase for the ball.
At times the Hatters looked in danger of being caught in possession around their own area but one confident move started with Sonny Bradley dancing his way out of danger at one end, and finished with the ball in the net at the other. Andrew Shinnie was the man to finish it off, curling home a sumptuous low strike which bounced off the inside of the post and in, beating Allsop at full-stretch.
The Hatters thought they had a second moments later but James Collins was flagged offside before lashing home, but the half-time whistle came at a good time for the visitors, who’d been in the game for most of the first period but found themselves gradually overpowered towards the interval.
But the start of the second half followed a similar pattern, with Blues indebted to Dominic Gape for a goalbound clearance from Sonny Bradley’s header, but the hosts then lost goalscorer Shinnie to injury, with Jorge Grant taking his place.
Curtis Thompson drilled a low shot wide from 20 yards as Wycombe looked to make the ball stick up front, and Dominic Gape was denied a clean connection with Alex Samuel’s low cross by a fine sliding tackle as he pulled the trigger.
Then Paris Cowan-Hall’s low shot was comfortably held by Shea before Allsop made a brilliant block from Elliot Lee’s point-blank effort at the end of a spell of pinball in the box from a Hatters corner.
Glen Rea miscued a header wide on 68 minutes before Gareth Ainsworth made a double change, introducing former Hatter Craig Mackail-Smith for Alex Samuel and Watford loanee Randell Williams for Paris Cowan-Hall.
But before long, the Chairboys’ challenge was made even tougher by Harry Cornick’s finish, gifted to him by Adam El-Abd’s wayward pass intended for Allsop, but seized upon by the Hatters frontman who made amends for his earlier missed chance.
Williams’ near-post drive threatened Shea who tipped the ball behind, before Marcus Bean saw yellow for a trip with Wycombe’s frustrations beginning to show.
Elliot Lee was almost just as frustrated when his goalbound shot was headed off the line by Curtis Thompson, but their place in the second round of the FA Cup rarely looked in doubt throughout the final 10 minutes, with their superb home record being cranked up another notch.
Scott Kashket came off the bench to replace Marcus Bean but had no opportunities to grab a consolation, though Mackail-Smith almost had a sight of goal against his former club but saw his opportunity snuffed out as he was set to pull the trigger.
Wanderers now look ahead to a first ever trip to Sunderland in the league next week.