Gary Alexander grabbed a hat-trick as Brentford won for the first time in eight matches to send Wycombe bottom.
Alexander scored with two headers from Jake Bidwell crosses either side of a close-range finish from Sam Saunders.
Dave Winfield headed in Grant Basey's free-kick but Toumani Diagouraga restored Brentford's three-goal lead, latching on to Marcus Bean's cross.
Ben Strevens converted Joel Grant's cut-back for 4-2 but Alexander sealed the victory with a stunning volley.
Alexander has now scored five goals in two matches after he grabbed a brace in the Bees' 3-2 defeat against Huddersfield on 21 January.
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Brentford manager Uwe Rosler told BBC London 94.9:
"We wanted to play a different way against them and I thought the tactics were spot on - the players executed the game plan perfectly.
"I'm very happy that the players had a break today as we've had an number of good performances and didn't get the rewards.
"We had a lot of up and downs but more ups than downs so I'm very happy for the players."