A hat-trick from Gary Alexander gave Brentford the points in an entertaining local derby at Griffin Park.
Sub-standard defending gave the Bees an unassailable lead at the break as crosses from both flanks allowed Alexander (two) and Sam Saunders to put the hosts in full control.
Dave Winfield gave Wycombe hope soon after the interval before Toumani Diagouraga restored the three-goal lead, and although Ben Strevens pulled one back, Alexander completed his treble with a fine volley at the back post.
Wanderers sunk to the bottom of npower League 1 as a result and have now conceded 16 goals in January, increasing the need for Gary Waddock to strengthen his squad before the transfer window closes on Tuesday night.
James Harper was handed his Wanderers debut following his loan move from Hull City, replacing Kadeem Harris (ankle) for the clash in West London.
After a flurry of half chances at both ends, Stuart Beavon created the best opening of the first 10 minutes when he left Harlee Dean for dead before forcing a smart save from Richard Lee.
But it was the hosts who took the lead on 11 minutes, Gary Alexander heading Jake Bidwell's pinpoint cross past Nikki Bull from eight yards.
And Uwe Rosler's men doubled their lead midway through the first half courtesy of Sam Saunders' low drive after Wanderers had failed to clear the danger.
Matters got even worse for Wycombe just before the half-hour mark, and it was a combination of Bidwell and Alexander who did the damage once again.
Bidwell whipped in another dangerous delivery from the left and Brentford's main man swept home from inside the six-yard box to put the hosts 3-0 up.
At the other end, Beavon saw a goalbound effort blocked by Toumani Diagouraga and Ben Strevens glanced a Danny Foster cross just past Lee's right-hand post as the Blues ended the half strongly.
Gareth Ainsworth came off the bench at the break to replace Stuart Lewis as Gary Waddock opted for a 4-4-2 formation, moving Strevens up front to partner Beavon.
And the first hint of a comeback arrived moments later when Dave Winfield rose highest to head home a superb delivery from Grant Basey. The linesman had initially flagged for a foul but the referee over-ruled him and the goal stood, giving hope to the vocal away following.
Ben Strevens then wasted a chance 20 yards out after Matt Bloomfield had robbed his man, before Sam Saunders' curling free-kick evaded everyone and bounced just wide of the far post at the other end.
James Harper then fired over the bar after great build-up play from Joel Grant and Beavon, while a left-footed cross-shot from Ainsworth almost found its way past Richard Lee with Strevens lurking for a possible rebound.
Matt Bloomfield fired high and wide and Dave Winfield denied Alexander a hat-trick inside the six-yard box as the chances kept on coming at both ends, with the Blues well and truly in the ascendancy.
However, the Bees extended their lead with 17 minutes when Alexander's shot was parried into the path of Marcus Bean, who returned the ball for Toumani Diagouraga to tap home.
The three-goal advantage survived just two minutes as Ben Strevens kept Wycombe in the game with a close-range finish from Joel Grant's cutback, only after Grant and Beavon had been denied by a fine double-save from Richard Lee.
Jonathan Douglas then hit the post with a curling effort with the outside of his boot before Alexander completed his trouble with a fine volley at the back post following a deep cross from the left.
It could have been worse when Myles Weston thundered an effort against the bar from distance, but by that point the game was well out of reach and the Blues move below Chesterfield on goal difference.