Gary Cahill capped a man of the match performance with an 88th minute winner to give Bolton their first Premier League victory of the season.
Tamir Cohen's well taken opening goal had given the Whites an early lead before it was cancelled out through a Younes Kaboul header on 25 minutes.
Five minutes before the interval, Matt Taylor converted from the spot after Kevin Davies had been fouled inside the penalty area by Tal Ben Haim.
A second half equaliser from Kevin Prince Boateng looked like Wanderers would be leaving Fratton Park with a point, up until Cahill's late header.
Gary Megson made two changes from the defeat at Liverpool with Gretar Steinsson and Mark Davies replacing the injured Johan Elmander and suspended Sean Davis.
Tamir Cohen's header on four minutes almost set Wanderers up and running for the afternoon. The Israel international - who netted in the match against Liverpool - timed his dart into the penalty to perfection, meeting Sam Rickett's cross with a meaty header. The positioning of David James was the only reason Bolton didn't go ahead as the England international parried the effort and gathered at the second attempt.
Tommy Smith was looking exceptionally lively on his home debut, causing a few problems for Gary Megson's side on the left wing. His acrobatic attempt from ten yards out was fractionally off-target, as was Jamie O'Hara's drive shortly after.
But despite the odd showing of productivity from the hosts, Bolton had definitely started the better team. Kevin Davies blazed wide and Matt Taylor, unusually, screwed a shot the wrong side of the post having been sent clear.
The warning signs had certainly been there for Pompey, and it was Wanderers' just rewards when they took the lead on 13 minutes. Having tested James already, Cohen made sure that his finish was out of reach of the Portsmouth stopper when the ball landed at his feet inside the penalty area. The left-foot shot had just as much quality as Gretar Steinsson's well disguised through ball - a move of pure quality from Gary Megson's side.
Matt Taylor volleyed wide as Wanderers pressed for a two-goal advantage, however the lead lasted just 12 minutes as Pompey got themselves level thanks to Younes Kaboul. Jamie O'Hara's in-swinging corner was met by the Frenchman, who guided his header low into the corner and out of the reach of Jussi Jaaskelainen.
Moments later and Portsmouth could have turned the scoreline completely on its head. Again it was Kaboul who towered to meet a corner, but unlike the goal, he towered to head wide from what was probably an easier opportunity.
Vanden Borre wasted a brisk counter attack with an overhit cross and Frederic Puquionne header over the bar when unmarked as Pompey put Wanderers on the back-foot following the equalising goal.
It had been a pulsating first half-hour of football at Fratton Park, and it showed no sign of relenting despite the warm conditions. Gary Cahill had to make a vital block to deny Boateng on the edge of the area and Smith clipped a shot wide before Wanderers regained the lead five minutes before the interval.
Tal Ben Haim - on his debut - sent former team mate Kevin Davies tumbling inside the box and referee Chris Foy had no hesitations in awarding a penalty. Matt Taylor sent David James the wrong way from the spot to score his second goal in three games against his former club.
Having been awarded a penalty against them just before half-time, the home supporters felt aggrieved that Chris Foy failed to give one in their favour just after the restart. Hesitation in defence between Jaaskelainen and Knight resulted in Smith taking a tumble, but the referee was unmoved despite the protests of the Pompey faithful.
Everything that Paul Hart's side were creating was from the boot of Nadir Belhadj on the left touchline. Wanderers dealt with every cross that the nippy Algerian delivered but one in particular on 60 minutes was only half cleared by Zat Knight. The ball landed at the feet of Michael Brown whose shot flew only a whisker over the crossbar via a deflection from Cohen.
Portsmouth's second equaliser of the afternoon did come four minutes later from the boot of debutant Boateng. O'Hara's shot was originally blocked inside a packed penalty box, and the former Tottenham midfielder seized on the rebound to fire low past the hand of Jaaskelainen.
Gary Megson's response was to introduce Ivan Klasnic and Chris Basham, only after Gary Cahill had made his third goal-saving tackle of the game and Kevin Davies had looped a header into the arms of James.
The pace of the game simmered in the final quarter, but with three minutes remaining, Cahill pounced to seal a thoroughly deserved win for Bolton.
A long throw from Samuel was headed by Klasnic and Basham before the big defender launched himself forward to nod past James from four yards out.
Portsmouth claimed that Matt Taylor was offside - but it didn't matter. The linesman hadn't raised his flag and Bolton had sealed their first Premier League win of the season.
Portsmouth: James, Kaboul, Mokoena, O'Hara (Yebda 71), Picquionne, Brown, Borre, Smith (Webber 84), Boateng, Ben Haim, Belhadj (Subs not used: Begovic, Mullins, Williamson, Utaka, Kanu)
Bolton: Jaaskelainen, Ricketts,(Klasnic 71) Knight, Cahill, Samuel, Steinsson, Mark Davies (Basham 71), Muamba, Cohen (McCann 79), Taylor, Kevin Davies (Subs not used: Al Habsi, Robinson, O'Brien, Chung-Yong)