John Mousinho’s men have a useful habit of battling back after conceding first and Wycombe became the latest – and sixth – league side to fall victim this term.
The Blues had been trailing after 58 minutes and failing to their first defeat of a campaign which has seen them top League One for several weeks.
Josh Scowen had capitalised on poor marking from the Chairboys’ only corner of the first half to break the deadlock in the 22nd minute.
It was very much against the run of play in a half the Blues dominated without truly putting the visitors keeper under any meaningful pressure.
Nonetheless, Pompey found a way back in the 58th minute when got to the byline to tee up Colby Bishop for the equaliser in front of a jubilant Fratton End.
As the match entered eight minutes of time added-on, it appeared the hosts would have to settle for a point, an outcome would have toppled them at the league summit with Oxford United winning against Shrewsbury.
However, in the eighth minute of extra-time, Jack Sparkes’ corner came in from the right and there was the magnificent Conor Shaughnessy to head home a winner.
How the Pompey contingent among the 17,450 crowd erupted as the Blues claimed a 2-1 victory at the death – and remained League One leaders.
In truth, until that point, Mousinho’s side had never quite done enough to capture the victory, despite some encouraging approach play and largely dominating play throughout.
Yet this team keeps digging themselves out of trouble, a handy characteristic which means they have now gone 22 league matches without defeat.
And, with 14 points gained from losing positions this season so far, that remains a brilliant habit.
With Marlon Pack missing through damage to his left ankle following Charlie Wyke’s red-carded challenge, it opened the door for Tino Anjorin for his full debut.
The Chelsea loanee has needed to be patient, restricted to bench duty and three substitute outings since arriving more than a month ago, but his chance had come.
Alex Robertson dropped deeper to partner Joe Morrell, creating an opening for the Chelsea loanee to operate behind Colby Bishop for his maiden Pompey start.
That represented the sole change to the side which won 2-1 at Wigan last weekend to maintain the Blues’ grasp on top spot.
Elsewhere, Ben Stevenson came onto the bench, while Morrell was handed the captain’s armband in Pack’s absence.
However, Connor Ogilvie, Kusini Yengi, Anthony Scully and Tom Lowery were still absent, along with skipper Pack.
It was a strong opening from the Blues, dominating the game, albeit without applying too much pressure on opposition keeper Max Stryjek.
Unsurprisingly they were full of confidence, providing the majority of attacking moments, although Garath McCleary did flash a shot past the far post during a breakaway on 17 minutes.
The deadlock was broken on 22 minutes following Luke Leahy’s corner from the right.
The ball was delivered to the near post, with Scowen getting in-between Bishop and Robertson to apply a touch high into the net to make it 1-0.
It was harsh on the hosts, yet, to their credit, picking themselves up to go again, once more dictating play, this time trying to find the leveller.
Crucially, though, they were short of genuine goal-scoring opportunities, with the Chairboys defending their box well and content to offer a threat on the occasional counter-attack.
There were no substitutions at the break as Pompey re-emerged to attack the Fratton Park in pursuit of a leveller to preserve their unbeaten record.
Anjorin had a glorious chance on 54 minutes when cutting in from the right after being fed by Rafferty, but his angled shot ballooned well over the bar.
That proved to be his final involvement, with Christian Saydee replacing the attacker in the 56th minute.
Within seconds he was involved in the build-up to a Pompey chance which should have been converted by Kamara.
Clever hold-up play and then a lay-off to Lane saw him fire in a low cross from the right which was knocked wide by the diving Norwich man at the far post.
Saydee’s introduction had lifted the Fratton faithful - and, on 58 minutes, it was 1-1.
Kamara initiated it, getting to the byline and knocking the ball into the six-yard box, where Bishop poked it among the legs for the equaliser.
Pompey had stepped up a gear and when Bishop produced an excellent cross from the right, Stryjek just got ahead of Kamara with a time aerial challenge.
Then Robertson collided with a Wycombe man going for the ball on the edge of the visitors’ box, earning him a booking - and, in the process, a one-match suspension in recognition of five yellow cards.
He was soon followed into the book by Poole, who poleaxed Scowan after mis-controlling a high ball, and another who must now serve a one-match ban.
On 78 minutes, Gavin Whyte was introduced for Lane on the right wing as the Blues went in search of a winner.
With full-time approaching, Shaughnessy connected with a free-kick from the left, but a deflection took the pace out of it and the keeper saved comfortably.
Then, at the death, Sparkes’ corner from the right was met by Shaughnessy ahead of the keeper to plant the ball into the net.
Victory was Pompey’s – and they remain League One leaders.