Wanderers exited the Carabao Cup at the first round stage, losing 4-2 on penalties to Brentford after a 1-1 draw at the Bees' new home.
Ethan Pinnock headed the hosts into a first-half lead but Wycombe overcame the adversity of losing Dominic Gape to a straight red card when debutant Daryl Horgan blased them level.
Nick Freeman and Scott Kashket missed their spot-kicks during the shootout and although Mathias Jensen was also wayward with his effort, Brentford edged through 4-2.
Brentford’s impressive new stadium was befitting of the fanfare of a packed house rather than the smattering of applause that greeted their arrival onto the pitch, but both clubs’ experiences – albeit with mixed results – of an empty house at Wembley two months earlier would’ve made it a not all too unfamiliar experience.
Josh Parker had the game’s first chance, diverting Joe Jacobson’s free-kick over the bar, and then Tariqe Fosu skewed his shot wide at the other end from Emiliano Marcondes’s cutback.
The Bees’ marquee summer signing Ivan Toney mistimed a header from Fosu’s cross, before Alex Samuel came inches away from connecting with Parker’s inviting cross from the right.
Matt Bloomfield drilled over the bar from 25 yards as Wycombe continued to look assured and confident against one of the second tier’s classiest operators last season, but they came unstuck from a routine free-kick when Ethan Pinnock found himself unmarked to head home the first competitive goal at the new stadium on 32 minutes.
Alex Samuel came close to a leveller with a superb touch, turn and shot from Ryan Allsop’s long kick, but Luke Daniels was equal to it down to his right, before Toney glanced a header wide from a dinked cross.
Dominic Gape saw a first-time shot blocked by Darius Charles before Allsop tipped Fosu’s side-footed effort over the bar as the half drew to a close, with the visitors feeling hard done by to be trailing at the interval.
Action resumed with no changes for either side, but Wanderers’ task was made more challenging when Dominic Gape was shown a straight red card for a challenge on Jan Zamburek.
Anthony Stewart produced a fine last-ditch tackle to prevent Toney a run at goal before Rico Henry lashed a shot wide from just outside the box as the Bees looked to make their extra man count, and Toney was again involved with a snapshot which was well kept out by Allsop.
At the other end, Josh Parker’s instinctive shot from out wide almost found its way past Daniels at his near post, but Brentford again took control and almost doubled their lead when Sergi Canos’ curling effort from the corner of the box landed inches wide.
Daryl Horgan was handed his debut on 64 minutes as he and Scott Kashket replaced Samuel and Parker in attack, and Fred Onyedinma followed soon after, taking David Wheeler’s place.
And before long, Wanderers were level. Pinnock’s pass was badly underhit and Kashket took full advantage, venturing goalwards and squaring for fellow sub Horgan to blast home from close range.
Brentford were almost the makers of their own downfall again, conceding possession sloppily to Horgan who picked out Onyedinma in space away to his left, but as the ball refused to sit kindly, the winger’s shot was kept out by Daniels.
Kashket then capitalised on a Charlie Goode mistake but couldn’t get his shot away, as Wycombe looked the more likely to find a winner before the full-time whistle sounded and the penalty shootout got underway.
Jacobson and Horgan found the net with their kicks, but Freeman and Kashket's misses proved costly as the Bees progressed.