They dominated most of the contest, with Jamal Lowe’s early finish added to by a Brett Pitman goal just after the interval.
Marcus Bean controversially reduced the deficit for the Chairboys, only for a fine free-kick from Pitman to restore the Blues’ commanding advantage.
A super strike from Scott Kashket ensured a nervy end to proceedings, but the visitors held on to secure the points.
Kenny Jackett made two changes from the side that beat Sunderland to lift the Checkatrade Trophy the previous week.
Oli Hawkins – who had struck the winning penalty in the shoot-out – was rewarded with a start, with Gareth Evans also returning, as Omar Bogle and Ronan Curtis dropped to the bench.
There were plenty of familiar faces in the opposition line-up, with Blues academy graduate Paris Cowan-Hall joining former Fratton loanees Ryan Allsop and Bean in the Wanderers team.
Pompey came racing out of the traps and won a series of early corners that kept the home defence on their toes.
The visitors were enjoying plenty of possession and territorial advantage, without being able to test Allsop between the sticks.
Pitman did well to race past Dominic Gape down the right and square for Lowe, who spun sharply and curled a shot over.
Another neat move saw Hawkins find Lowe with a cross-field pass and the winger laid the ball off for Pitman to fire just off target.
Allsop was then called into action for the first time, although was not overly troubled by a drilled effort from Lee Brown.
He could do nothing to stop Pompey from taking the lead on 18 minutes, however, as they finally made their pressure count.
A free-kick from Evans was not properly dealt with and when Matt Clarke lifted the ball back into the box, LOWE was there to drill it through a sea of bodies and into the net.
They did not sit back on their lead, though, and a shot from Ben Close was blocked after Tom Naylor had stolen possession.
Wycombe had offered little at the other end of the pitch, but had two great chances to level before the break.
The first opportunity came from a 25-yard free-kick after Alex Samuel had been fouled by Christian Burgess and Craig MacGillivray flung himself to the left to push behind Jason McCarthy’s attempt.
And the keeper made another fine save moments later, this time to keep out a fierce strike from Cowan-Hall.
But Pompey might have extended their advantage in stoppage-time, as Clarke teed-up Lowe for a curling shot that was well saved by Allsop.
Wycombe Wanderers 0
A second goal did arrive just 27 seconds after the restart, however, as Evans played a dangerous ball down the middle.
Anthony Stewart looked like he would deal with it, but PITMAN nipped in to steal the ball and confidently slot it home.
Rather then dent Wycombe’s confidence, though, it seemed to spark them into life and the hosts suddenly enjoyed a spell of pressure.
And they made the most of it by reducing the deficit through Bean’s close-range finish, although referee John Busby had a lengthy discussion with his assistant before allowing the goal to stand.
The Blues were adamant that the midfielder had been in an offside position, although the official seemed to think the ball had come off a white-shirted player.
It had been a frantic start to the second period and Pompey had a chance to restore their two-goal advantage when Evans was brought down by Stewart just outside the box.
PITMAN stepped up to take the free-kick and curled a fine effort past Allsop’s desperate grasp to spark more scenes of joy in the packed away end.
Both teams were looking capable of adding to the scoring as the action continued to switch from one end to the other.
Pitman’s pass was cleared before it could reach Clarke at the near post, while substitute Adebayo Akinfenwa headed over.
But it took another fine save from MacGillivray to deny the Chairboys on 72 minutes, with the keeper getting down to push clear Samuel’s shot.
Pitman received a standing ovation as he made way off the pitch, with Anton Walkes coming on for the closing stages.
It was the hosts cheering soon after, though, as Kashket reduced their deficit with a screaming shot from just inside that area that flew into the top corner.
Curtis then replaced Evans, as Jackett looked for his side to get back on track, although the Chairboys came close to a leveller when Samuel’s header flashed past the post.
Wycombe were given renewed hope when the fourth official displayed six minutes of time to be added on.
The hosts continued to try to pump the ball into the Blues box, but the visitors held firm to close the gap on second-placed Barnsley.
Wycombe (4-1-4-1): Allsop; McCarthy, El-Abd (c), Stewart, Harriman; Gape; Cowan-Hall (Kashket 74), Bean (Akinfenwa 61), Bloomfield (Thompson 43), Freeman; Samuel
Goals: Bean 54, Kashket 82
Subs not used: Ma-Kalambay, Jombati, Jacobson, Owens
Pompey (4-2-3-1): MacGillivray; Thompson, Burgess, Clarke, Brown; Naylor, Close; Lowe, Pitman (c) (Walkes 81), Evans (Curtis 84); Hawkins
Goals: Lowe 18, Pitman 46, 60
Subs not used: Bass, Haunstrup, Morris, Vaughan, Bogle
Referee: John Busby
Attendance: 6,978 (1,810 Pompey fans)