Pompey produced a poor performance at Wycombe to suffer their first defeat for seven weeks.
The impressive Anis Mehmeti gave the hosts an early lead and although the Blues were better after the break, Garath McCleary struck late on to dent any hopes of a comeback.
Danny Cowley made three changes from the side that knocked MK Dons out of the FA Cup the previous weekend.
Dane Scarlett and Owen Dale both returned after being ineligible for the second round tie, while there was also a spot for Connor Ogilvie.
Reeco Hackett and Denver Hume dropped to the bench, while Zak Swanson was missing from the squad altogether.
There was a place among the substitutes for Joe Morrell following his return from Qatar, where the midfielder featured for Wales at the World Cup.
Plenty of noise was emanating from the sold out away end when the action began, but it was the hosts who made the brighter starter.
A cut-back from Anis Mehmeti was only partially cleared and Josh Scowen blazed the loose ball high over the bar.
They did break the deadlock on 14 minutes, however, and it came from a long kick up the pitch by keeper Max Stryjek.
The ball was brought down brilliantly by former Blues loanee David Wheeler and helped on by Brandon Hanlan for Mehmeti to lash home a fine finish.
He might have had a second goal midway through the first half, but scuffed his shot straight at Josh Griffiths after the ball had dropped kindly for the winger.
Pompey then began to mount a recovery, however, and carved open some decent chances of their own.
There was an almighty scramble in the Chairboys box, but the ball would not land kindly for a mint-shirted player.
Ronan Curtis tried to attack the ball and appeared to be booted by Lewis Wing, with referee Scott Oldham ignoring the penalty appeals.
A quick break was then launched by Curtis and he tried to exchange passes with Scarlett, but the return ball was just too heavy.
But Wycombe then finished the half with a flourish and when a free-kick was only cleared as far as Alfie Mawson, he smashed a shot against the post.
Half Time: Wycombe 1 Pompey 0
Cowley’s response was to make a double substitution at the break, as Curtis and Jay Mingi made way for Hackett and Ryan Tunnicliffe.
Pompey were looking to put up more of a fight and tried their best to find a route through the resolute Wanderers defence.
Once passage of passing play did lead to an opening, but Dale could not keep his shot down to test Stryjek.
Not that there was much to trouble Griffiths at the other end, with McCleary angling the ball over after being teed-up by Mehmeti.
A third change followed for the visitors for 66 minutes, as Ogilvie made way for Hume in the left wing-back role.
The Blues remained on the hunt for a breakthrough and when Colby Bishop met a Clark Robertson corner, Hackett could not manage to scramble the ball over the line.
Scarlett and Hackett then both drew saves from Stryjek in quick succession, the latter an instinctive effort down to the keeper’s right.
Robertson’s fine cross from the left was then met by a diving Scarlett header, but again Stryjek was equal to it.
Pompey still had to be alert at the other end and Griffiths did well to keep the ball out when Sam Vokes flicked a low Jack Grimmer centre towards the net.
But they needed to make an impact at the other end, with Josh Koroma coming on for Michael Morrison for the closing stages.
Griffiths was called upon again on 86 minutes, though, spreading himself to deny Wing after the midfielder had been sent through on goal.
He could not stop the hosts from wrapping up all three points moments later, however, as McCleary charged in from the left to get on the end of Mehmeti’s pass and put the game to bed.
Wycombe (4-2-3-1): Stryjek; Grimmer, Mawson (c), Tafazolli, Obita; Wing (Freeman 90), Scowen; Wheeler, Mehmeti, McCleary; Hanlan (Vokes 79)
Goals: Mehmeti 14, McCleary 88
Booked: Mawson
Subs not used: Dickinson, McCarthy, Horgan, Al-Hamadi, Kaikai
Pompey (3-4-1-2): Griffiths; Morrison (Koroma 84), Raggett, Robertson (c); Dale, Mingi (Tunnicliffe 46), Pack, Ogilvie (Hume 66); Curtis (Hackett 46); Scarlett, Bishop
Booked: Ogilvie, Robertson
Subs not used: Oluwayemi, Morrell, Pigott
Referee: Scott Oldham
Attendance: 6,306 (1,828 Pompey fans)