Second-half goals from David Nugent and David Cotterill gave Portsmouth the points in front of the biggest League attendance at Portman Road this season.
A crowd of over 23,000 watched Town carve out a string of chances, with Gareth McAuley, Connor Wickham and Jason Scotland all going close before Pompey went ahead on 55 minutes through Blues' nemesis Nugent.
The England international took his goal tally to eight goals in seven visits to Portman Road with a right foot drive and then set up Cotterill with a slide rule pass for the second goal 15 minutes from time.
Town made one change from the team that went down at QPR in midweek, David Norris returning from injury to replace torn stomach muscle victim Colin Healy.
Hermann Hreidarsson was back at Portman Road and was immediately in the action, making a block as Lee Martin got down the right.
Martin carried the main threat for Town in the opening half, the former Manchester United winger dragging his shot wide after turning away from his marker, then teeing up Grant Leadbitter whose shot was blocked, the ball then cannoning back off the midfielder and going wide.
On 10 minutes Jimmy Bullard sent a corner arrowed in to McAuley and his header looked destined for the net until it hit Scotland on the line and rebounded wide.
Another Martin cross set up Leadbitter who couldn't control his volley, then Carlos Edwards got in on the act down the right flank, his delivery just beating Wickham at the far post.
The England U21 international should have put Town ahead before the midway point in the half, Edwards the provider with another right wing delivery - the ball falling at the 17-year-old's feet eight yards out but Jamie Ashdown denied the Blues' frontman.
Ricardo Rocha picked up the first yellow card of the game for a foul on Norris as Portsmouth struggled to weather the early Town storm, Scotland going close again with a header from Bullard's free-kick.
Edwards dragged a shot wide, Wickham then heading over from Martin's cross before Pompey got their first sight at goal on 37 minutes - Dave Kitson denied by Marton Fulop's left foot in the clearest chance of the half.
Pompey finished the half on the front foot, catching Blues on the counter on a couple of occasions, Damien Delaney clearing the danger from Cotterill's cross, then Kitson almost getting in again.
Wickham headed over with the last chance of the half with the goal open and the crowd on their feet in expectation, a raised flag from the referee's assistant raising a doubt if the ball had hit the net.
Paul Jewell's side started the second-half as they had the first and Wickham met Edwards' cross perfectly 60 seconds after the restart but his header went straight at Ashdown.
The Pompey 'keeper held firm from Scotland's strike after Edwards had set him up, the Town frontman then driving a left foot effort inches wide.
Portsmouth got the breakthrough on 55 minutes, Nugent cutting inside Norris after a Cotterill free-kick had failed to be dealt with and blasted the ball past Fulop from 15 yards.
Aaron Mokoena replaced Ward on 66 minutes in the first change of the game, the midfielder immediately tidying up at the back as Wickham threatened.
Town made a double change for the last 20 minutes, Andy Drury on for Norris and Luciano Civelli for Scotland.
Ashdown prevented Civelli announcing his arrival with a goal, the 'keeper holding on to Leadbitter's cross aimed at the Argentine.
Pompey extended the lead on 76 minutes, Fulop failed to get yardage with his clearance, Drury lost out in midfield and Cotterill took advantage to find the net from Nugent's pass.
Town made a final change with Tamas Priskin on for Martin for the final exchanges, Leadbitter then testing Ashdown from distance.
A brilliant tackle six yards out by Ritchie De Laet robbed Priskin when he looked certain to score, Town fans calling for a penalty but to no avail in an incident that summed up Blues' frustration on the day as Paul Jewell tasted home defeat for the first time as Town boss.
Town: Fulop, Edwards, McAuley, Delaney, Kennedy, Martin (Priskin 83), Norris (Drury 73), Bullard, Leadbitter, Wickham, Scotland (Civelli 73). Subs not used: Lee-Barrett, Peters, Smith, O'Dea.
Portsmouth: Ashdown, De Laet, Halford, Rocha, Hreidarsson, Hogg, Mullins (Kanu 90), Cotterill, Ward (Mokoena 66), Nugent (Dickinson 90), Kitson. Subs not used: Flahavan, Ciftci, Kilbey. Booked: Rocha.