It was a sad return to Colchester for Rangers' caretaker boss Mick Harford, who was the assistant to Geraint Williams at Layer Road up until this summer.
QPR looked excellent going forward and Colchester old boys Hogan Ephraim and Rowan Vine both struck against their former club.
But once again, the Londoners' leaky defence was their downfall and they are still waiting for their first victory of the season.
The visitors were not helped by an own goal in the 19th minute.
A cross-cum-shot from Mark Yeates was deflected on to the woodwork by keeper Lee Camp, only for centre-half Mikele Leigertwood to bundle the loose ball into his own net while under pressure from Kevin Lisbie.
QPR were level just before the half-hour mark when Ephraim ran on to Vine's pass to slot past keeper Dean Gerken.
But their joy lasted only a minute as Kemal Izzet headed home a cross by Danny Granville to restore Colchester's lead.
An in-form Yeates hit the target with a deflected free-kick on 38 minutes to give the U's a 3-1 lead at the break, but the goals continued to flow in the second half.
Rangers were given hope when Vine, who had signed on loan from Birmingham on Tuesday, beat Gerken with a snapshot following a strong run by Gareth Ainsworth.
However, Colchester made the game safe in the 63rd minute.
Lisbie's curling shot struck the far post, but Izzet swung a cross back into the danger zone for Clive Platt to head home his second goal for the U's since his summer move from MK dons.
This was Colchester's first home win of the season and it lifted them up eight places in the table to 12th spot.