Charlie Austin tapped in from close range in the first half and Macauley Bonne added a late second, putting a stop to the Town’s magnificent midweek home record in the league - 22 games unbeaten - a run which dates back to January 2018.
Manager Nathan Jones made three changes to the side that defeated Bristol City in the league prior to the turn of the year, including a second league start of the season for Kazenga LuaLua.
The Hatters found it tricky to contain Queens Park Rangers in the first half as Simon Sluga was tested a number of times, key to thwarting their initial attacking intent.
Early on, the Croatian international parried Bright Osayi-Samuel’s fierce shot away from goal, before crucially denying Lyndon Dykes who rushed down on goal half-an-hour into proceedings.
But Sluga was unable to preserve his clean sheet as QPR found the breakthrough six minutes from time in the first period.
Charlie Austin marked his second Hoops debut with a goal from close range, tapping home following Geoff Cameron’s flick-on from Ilias Chair’s corner.
The Hatters immediately had an opportunity to find an equaliser as the second half began.
QPR’s intended clearance rebounded off Austin which allowed Collins to run through on goal, however, the usually composed striker failed to hit the target, a let-off for the away side.
Town created better openings for themselves and came closest to replying in the 70th minute, when Pelly-Ruddock Mpanzu hit the outside of the post.
Harry Cornick played the ball inside to Kiernan Dewsbury-Hall, who in turn released a quick ball to his team-mate, but Mpanzu’s curler was just wide of the mark.
Jones rolled the dice with a triple change inside the last ten minutes and Dewsbury-Hall had a late effort well-saved, before Rangers put the game beyond doubt, scoring a second through substitute Macauley Bonne.
Looking ahead, the Hatters will look to put loss behind them when they travel to Vitality Stadium to face second place Bournemouth on Saturday.
Town: Sluga; Bree, Lockyer, Bradley (C), Potts (Nombe 77); Rea, Mpanzu (Berry 83), Dewsbury-Hall; Cornick, LuaLua (Moncur 83), Collins (Hylton 83).
Subs not used: Shea, Tunnicliffe, Clark, Kioso, Galloway.
QPR: Dieng; Kane, Barbet, Cameron (C), Dickie; Ball, Carroll, Chair (Adomah 75), Osayi-Samuel; Dykes (Kelman 90+3), Austin (Bonne 59).
Subs not used: Lumley, Thomas, Willock, Hamalalinen, Bettache.
Goals: Austin (39), Bonne (89)
Yellows: Bonne
Referee: Andy Woolmer