Wanderers had more chances than the home team, but could not find the net and were made to pay.
Wycombe suffered a blow even before the kick-off when defender Tom Williams complained of chest pains in the warm-up. The club took advice from a doctor and in the end decided to leave him on the bench with Sam Stockley drafted in.
It was no surprise that Chesterfield dominated the opening 20 minutes, but once Wycombe settled down they created chances.
Sergio Torres broke down the middle and found Scott McGleish, but with two team-mates in good positions the striker chose to go it alone and sent his shot well over the bar.
Wycombe got through again in the 23rd minute when Jermaine Easter blasted in a shot which was blocked by defender Aaron Downes. The ball came back to McGleish, but his effort was saved at point-blank range by Chesterfield keeper Barry Roche.
Wycombe looked dangerous again in the 32nd minute when Torres went on a 55-yard run down the left, but his cross was too powerful for McGleish.
Chesterfield were slightly fortunate to be in front at half-time, thanks to a 44th minute goal. A free-kick from Phil Picken was only half-cleared by the Wycombe defence and Derek Niven rammed his shot into the bottom corner.
Wycombe had another clear-cut chance in the 54th minute when McGleish got behind the Chesterfield defence, but with the keeper off his line, could only shoot wide.
Martin Bullock, who was lively throughout the game, then opened up the Chesterfield defence with a cross from the right, but neither Easter nor McGleish could make contact.
In the 71st minute Easter had a clear-cut chance to equalise after being put through by Bullock, but blasted his first-time shot wide.
Three minutes later, Chesterfield grabbed their second of the game to seal the points. Niven sent a cross into the box, which was missed by Wycombe keeper Scott Shearer and Jack Lester headed in a simple goal.