Tonda Eckert made three changes to the team that started on Wednesday in the home win against Sheffield United. Southampton hadn't won at Fratton Park in the league since 1976 before today's match.
Sticking with a 4-2-3-1 formation, the Saints looked more balanced from front to back. James Bree started the match at right back, with Matsuki a surprising starter ahead of Tom Fellows.
Jack Stephens kept his place at centre-back alongside Taylor Harwood-Bellis, displacing both Nathan Wood and Joshua Quarshie.
Wantaway striker, Adam Armstrong, returned at the expense of Ross Stewart, who played sixty minutes on Wednesday night.
Saints unlucky not to be ahead early
Portsmouth v Southampton - Sky Bet Championship - Fratton Park | Andrew Matthews - PA Images/GettyImages
Southampton were unlucky not to be ahead in the eleventh minute when Finn Azaz slid Adam Armstrong in. Armstrong kept his shot down from 12 yards out but was unable to steer the ball wide of the keeper, who saved well with his feet.
Only a great save by Nicolas Schmid in the nineteenth minute denied Armstrong again. The Saints striker struck his volley well from close range, but the Pompey keeper did well to make a reaction save.
Millenic Alli shot tamely wide for Portsmouth in the 22nd minute when he should really have hit the target.
Welington was in the wars in the first half; a nosebleed forced him off for a few minutes. He made an excellent block on a Chaplin volley midway through the first period, deflecting the ball over the bar for a corner.
Jack Stephens made an excellent challenge to deny Colby Bishop a certain goal, a reminder of the threat that Portsmouth possess.
Robust in the challenge but devoid of good possession
Portsmouth v Southampton - Sky Bet Championship - Fratton Park | Andrew Matthews - PA Images/GettyImages
Southampton were robust in the challenge throughout the first half, but unable to get control of possession.
Portsmouth had nine shots compared to Southampton's three in the first half. However, Saints created the better chances and hit the target twice.
Pompey's efforts, in contrast, were a weak header that looped up into Peretz's hands and a blocked volley.
Half-Time: Portsmouth 0-0 Southampton
Both teams were unchanged at the start of the second half, which Southampton started strongly before Connor Ogilvie went straight through the back of Kuryu Matsuki without picking up a yellow card.
Finn Azaz should have done much better from 17 yards out, seven minutes into the second half. His scuffed effort went through Adam Armstrong's legs but directly into Schmid's arms in the Pompey goal.
Léo Scienza put Saints ahead in the 57th minute, finishing coolly after being put through by Finn Azaz. After running the full-length of the pitch, Scienza danced in front of the joyous Southampton fans in the away end.
Portsmouth 0-1 Southampton
No quarter was given when Flynn Downes and Connor Ogilvie flew into a 50:50 challenge a few minutes later. Ogilvie was left hobbling away from the challenge as Downes skipped away.
Azaz and Matsuki were withdrawn at the hour mark, and Tom Fellows and Shea Charles were introduced.
After sixty-five minutes, Jay Robinson and Ross Stewart were introduced at the expense of Scienza and Armstrong, respectively.
With twenty minutes left on the clock, things boiled over when an overzealous tackle by Downes resulted in Zak Swanson squaring up to each other. Both were booked.
Portsmouth drew level in the 76th minute as Southampton conceded from another set piece when Ebou Adams bundled in from under the bar. The ball looked to have come off Adam's hand, but the Saints will be disappointed that the corner wasn't dealt with in the first place.
Portsmouth 1-1 Southampton
Southampton dropped deeper as full-time approached, and Portsmouth went for the winner. Shea Charles added composure to the midfield, but the other three substitutes failed to get into the game for Southampton.
Harwood-Bellis and Daniel Peretz made last-ditch clearances in added time, but Portsmouth were unable to convert their pressure into a goal as the points were shared.