Wanderers put in an improved display from Saturday when they faced Fulham and frustrated the Premier League side for long periods of the game.
Adel Taarabt curled just over the bar after five minutes before Shaun Wright-Phillips cut inside and drilled wide as the visitors started brightly.
Nikki Bull saved smartly low to his left after Jamie Mackie had headed Armand Traore’s left-wing cross goalwards, but the Blues improved and Richard Logan saw an effort blocked on the edge of the area.
Bull did well again in the 27th minute when he kept out Djibril Cisse’s powerful strike with his legs, but Wycombe’s keeper could do nothing three minutes later when the visitors opened the scoring.
Taarabt turned away from Matt Bloomfield in the centre of midfield before finding Mackie with a pin-point crossfield ball. The Scottish international cut inside Charles Dunne and found the bottom left corner from 10 yards.
Lee Angol shot wide following good play from Joel Grant and Marvin McCoy and came close to equalising three minutes before the break, but Rob Green kept out his low effort.
Wycombe started the second half brightly and Grant came close to finding the bottom corner after cutting in from the right and striking left-footed.
However, Gary Waddock’s side were almost 2-0 behind in the 55th minute and were saved by Marvin McCoy, who recovered well to clear Shaun Wright-Phillips’ effort off the line.
The lively Grant shot straight at Green before Gareth Ainsworth was introduced in the 64th minute to the loudest cheer of the night.
QPR doubled their advantage 20 minutes from time when Wright-Phillips latched on to Hogan Ephraim’s through ball and beat Dunne before rounding Bull and slotting into an empty net.
Bull produced two fine saves to deny Andy Johnson in quick succession and then performed heroics to keep out Bobby Zamora.
Substitute Matt Ingram produced a fine flying save to tip Eprhaim’s long-ranger over the bar, but could do nothing as Nedum Onouha powerefully headed home the resulting corner four minutes from time.
Wycombe: Bull (Ingram 81), McCoy, Dunne (Wood 79), Doherty (c) (Basey 46), Stewart (Hause 83), Grant, Lewis (Spring 46), Bloomfield, Angol (Ainsworth 64), Oli (McClure 46), Logan (Beavon 46).
QPR: Green, Onouha, Traore (Ephraim 34), Ferdinand, Hill, Mackie (Johnson 62), Park (Derry 73), Fabio, Wright-Phillips (Doughty 90), Taarabt (Dyer 73), Cisse (Zamora 62).
Subs: Murphy, Ehmer, Connolly, Harriman.