Wolves are now hot favourites to reach the First Division play-offs for the third time in five years after taking full advantage of another slip-up by arch rivals Sheffield United.
But Colin Lee's side had to work hard and display plenty of patience to break down a Portsmouth side who arrived at Molineaux with nothing more than survival on their minds.
Alan Ball sent his side out with a packed defence and, for 72 minutes, his players kept Wolves at bay without too much trouble.
But the 58th minute sending-off of mid-fielder Jeff Peron handed Wolves a vital initiative which they capitalised on in much the same way as they had when beating 10-man Crewe in midweek.
Wolves had hardly threatened in the second half and their supporters were showing increasing signs of frustration.
But the breakthrough finally came 18 minutes from time when a short corner found full-back Kevin Muscat, who thundered a tremendous low drive through a crowded area from more than 20 yards.
Three minutes later, the game was as good as over when veteran Pompey keeper Alan Knight inexplicably picked up back-pass just inside his area and left Simon Osborn to roll a short free-kick which Havard Flo blasted past the visiting wall into the net.
It was the big Norwegian's fourth goal in three home matches and meant there was no way back for a Portsmouth team who had started with only Steve Claridge in attack.
The former Wolves striker, booed every time he touched the ball, went as close as anyone in his side to pinching a goal on the break in the first half when he chipped a couple of feet over the bar from outside the area following a mistake by Dean Richards.
Claridge was later booked for dissent as Wolves monopolised possession without possessing the guile to open up Pompey's rear guard.
Carl Robinson missed the target from a couple of reasonable chances while Flo saw a promising header turned over his own bar by Alan McLoughlin.
The second half appeared to be going very much to Portsmouth's satisfaction until Peron, already booked for a foul on Osborn, foolishly pulled back Muscat just outside the area.
That left Wolves with 32 minutes to break down a side weakened by a red card and the pressure quickly built up.
Neil Emblen and Steve Sedgley missed the target from 20 yards and Flo saw a header bravely blocked by Adrian Whitbread.
But the breakthrough came shortly afterwards and Wolves finished well in command, their propspects further improved by Sheffield's defeat at Barnsley.
Pompey should have pulled one back when substitute Thomas Thogersen fired wide with only Mike Stowell to beat.