After Tom Eaves missed a glorious chance inside the opening five minutes, the visitors were made to pay for that miss after 14 minutes when Gareth Evans converted from the penalty spot.
Trailing at the break the Glovers were level on 51 minutes when Francois Zoko levelled the scores capitalising on hesitancy in defence.
But Pompey made sure their automatic promotion chase stayed on track with two goals in 10 minutes courtesy of Kal Naismith and substitute Jamal Lowe.
Darren Way made three changes from the side that lost at home to Carlisle United seven days ago, with two forced alterations.
Captain Ryan Dickson (ankle) and Shayon Harrison (ill) were ruled out allowing Tom James and Brandon Goodship to make their first league starts of the season.
Without the suspended Ben Whitfield, Matty Dolan’s return from an ankle knock proved timely as he went straight back into the Glovers midfield, whilst Otis Khan returned on the bench after three months sidelined with an ankle ligament injury.
Bathed in sunshine and welcomed onto the pitch by close to 18,000 supporters, Town wasted no time in announcing their arrival with a neat move inside the opening five minutes.
Intricate passing engineered captain Kevin Dawson space wide on the right, but his inch-perfect cross could only be headed over by Eaves, grazing the bar on its way over.
Looking to irradiate any early nerves that Yeovil chance may have created, Pompey soon went close themselves as Matt Clarke’s header from a corner was cleared off the line by Liam Shephard with just six minutes on the clock.
In a frantic start to proceedings, an already vocal home crowd were even more vociferous when Bevis Mugabi’s foul on Gary Roberts inside the box saw referee Graham Horwood point to the spot.
Having missed their last six spot kicks Evans stepped up and coolly converted from 12 yards to give Paul Cook’s side the lead with less than 15 minutes played.
If much of Pompey’s attacking play was fluent, their chance to double the lead was anything but.
Roberts’ cross from the left looped up off Mugabi, meaning Artur Krysiak could only watch as the ball cannoned off of the post and bounced away from danger.
Having ridden the pressure that followed the promotion chasers taking the lead, it took the Glovers until 34 minutes to come close to levelling the scores.
Looking to make amends for his mistake at the other end, Mugabi was only left frustrated in the Pompey box as his header from Dolan’s corner flew just wide.
That was as close as either side came to scoring in the final 10 minutes of the half, with Town enjoying an even share of possession as proceedings were halted to allow for a break.
Mirroring the frantic start to the first-half the second 45 got underway in similar fashion, this time with roles reversed.
Whilst Yeovil missed a good chance early on it was Portsmouth’s turn with 50 minutes played, as Naismith’s header from close range was kept out by a superb Krysiak reaction save.
Before many of the 17,600 home faithful could re-take their seats from that opportunity Way’s side drew level in fortuitous fashion.
Under pressure from Zoko in the box Enda Stevens could only rush a clearance with the Town striker getting a toe to the ball to see it loop over David Forde for his 12th goal of the season.
Desperate to not drop points in the closing stages of their promotion push, Pompey turned up the pressure on the Green and Whites, immediately penning themselves in the Glovers half.
A shaky five minutes defensively saw the experienced Nathan Smith introduced for Mugabi just before the hour-mark, but it wasn’t enough to stop Paul Cook’s side re-taking the lead.
With 68 minutes on the clock the pressure told as Naismith picked out the bottom corner from Stevens’ cut-back, before Lowe made an instant impact from the bench with a low finish from an acute angle to kill off any hopes of a dramatic Yeovil comeback.
The Glovers threw numbers forward in the closing stages in search of some late drama, but Pompey killed the game to record a seventh win in 11 games, condemning Town to consecutive defeats.
Portsmouth: Forde; Evans, Burgess, Clarke, Stevens; Rose, Doyle; Bennett, Roberts (Chaplin 67’), Baker (Lowe 76’); Naismith (Kabamba 89’).
Subs not used: O’Brien, Whatmough, Linganzi, Talbot.
Yeovil Town: Krysiak; Mugabi (Smith 57’), Lacey, Butcher; Shephard, Dawson, Dolan, James; Goodship (Khan 70’), Zoko, Eaves (Akpa Akpro 50’).
Subs not used: Maddison, Lawless, Jones, Sowunmi.