Tony Thorpe netted the first goals of his QPR career to see off the Spireites.
Chesterfield had chances a plenty but recent signing Thorpe's cool finishing put Rangers in the driving seat before Paul Furlong's late goal sealed a fine win for the home team.
The Spireites lost Steve Payne after he suffered a head injury in an early collision with Gareth Ainsworth. Worse followed for Roy McFarland's side when Thorpe put Rangers ahead in the 29th minute.
Thorpe took Furlong's smart lay-off in his stride before firing past goalkeeper Carl Muggleton from the edge of the area.
A Rangers goal had been on the cards. Muggleton earlier saved from Thorpe after the striker got his head to Kevin McLeod's cross, before Martin Rowlands cleverly lifted the ball over Chesterfield's Chris Brandon and volleyed just over from long range.
There was no escape for the visitors when Thorpe hit the net, but Chesterfield missed several good chances to equalise early in the second half.
Caleb Folan, who replaced Payne, found himself through on goal less than a minute after the break, but Rangers' keeper Chris Day saved his shot and then reacted quickly to keep out Brandon's follow-up and complete a fine double stop.
Moments later, Day tipped away Mark Hudson's header, before Spireites striker Glynn Hurst sent a shot over the bar.
Chesterfield continued to put Rangers under pressure and after Folan headed wide, Day saved Mark Allott's header.
Then Thorpe scored his and Rangers' second completely against the run of play in the 67th minute.
Tommy Williams threaded the ball through and Thorpe calmly netted with a right-foot finish.
Thorpe missed a great opportunity to claim a hat-trick when he headed McLeod's cross over.
But Furlong made no mistake with a superb 25-yard free-kick three minutes from the end.
McFarland admitted: "We had several good chances and didn't score any of them, which is very disappointing.
"We lost the game through our own fault, rather than QPR playing through us."