Scott Kashket’s massively-deflected goal inflicted a second successive defeat on Pompey.
Wycombe’s leading scorer provided the decisive moment on 48 minutes, the ricochet off a Blues leg wrong-footing David Forde.
It was so harsh on Paul Cook’s men, who deserved something from the Adams Park visit this afternoon.
Yet despite a spirited late charge, there was to be no leveller for the visitors on another disappointing afternoon.
Cook had made five changes to the side which lost against Exeter last weekend in disappointing fashion.
That meant a debut for Eoin Doyle, while there were recalls for Gary Roberts, Kyle Bennett and Amine Linganzi.
There was also a full debut for Jamal Lowe, with Michael Smith, Carl Baker, Danny Rose, Conor Chaplin and Kal Naismith dropping out.
Lowe could have broken the deadlock after only 10 seconds when he dragged a left-foot shot wide when extremely well-placed.
In a largely tight first-half, a moment of quality from Lowe on 31 minutes saw him put the ball through the legs of Anthony Stewart and spin round to get ahead of the defender.
However, the striker’s left-foot shot lacked power and was straight at the keeper.
Then Bennett put Enda Stevens through down the left but once more the angled shot was at Jamal Blackman.
Yet Wycombe broke the deadlock on 48 minutes when Kashket’s shot took a wicked deflection off a Pompey to wrongfoot David Forde and trickle into the net.
Substitute Carl Baker then lofted a shot over the bar and also went close during eight minutes of time added on.
However, an equaliser eluded Pompey and they slipped to a consecutive defeat to play-off and promotion rivals.