Martin Paterson and Charlie Austin returned to action as second-half substitutes but the good news ended there for the Clarets as they were sunk by an injury-time winner.
Paterson's first taste of action since the opening day of the season and Austin's comeback from a further shoulder dislocation hinted at better things to come.
But with neither able to conjure up an instant goal, below-par Burnley left themselves susceptible to the last-gasp strike David Norris delivered to give Pompey their first away win of the season.
Portsmouth will feel they were worthy of some reward at a ground where they haven't lost since 1982 but for Burnley this was a distinct let-down as they missed out on the chance to record a fourth successive league win for the first time in six years.
Eddie Howe's side were looking to continue their climb up the table but the vulnerability they have shown at Turf Moor surfaced again as they were beaten at home for the fifth time this season.
Kieran Trippier blocks an early chance for Luke Varney
With Sam Vokes back in the starting line-up following his winner at West Ham, the Clarets reverted to their favoured 4-4-2 formation for home games with Junior Stanislas preferred to Keith Treacy on the opposite flank to the recalled Ross Wallace.
But any attacking threat was sadly absent in a dismal first half totally devoid of chances for Howe's mis-firing side.
Pompey didn't do much more but looked comfortable for a team with such a dismal away record and did suggest they might create something on the break.
Twice in the opening quarter of an hour Luke Varney had chances to put the visitors in front but was too slow to react after Lee Grant had palmed out a Norris shot at full stretch and then just failed to cleanly beat Grant to a Norris through-ball before being bizarrely penalised for a foul.
Chris McCann offers a rare threat
The Pompey forward was injured in the process and subsequently hobbled off but missed nothing as he headed for the showers, bar a shot from Hayden Mullins which Grant fumbled but managed to keep out from the only meaningful effort on target of the half.
As long as they didn't concede, things could only get better for Burnley and within five minutes of the re-start they produced their best moment yet as Chris McCann almost put the Clarets in front.
Michael Duff's ball forward allowed Vokes to dummy for Jay Rodriguez to lay the ball into the path of McCann, whose blistering drive was just about touched over the top by goalkeeper Stephen Henderson.
Pompey's response came from Eric Huseklepp, who volleyed just wide, and with almost an hour gone, Howe turned to Paterson to try and spark the Clarets into life.
Martin Paterson's return was a plus point for the Clarets
Paterson was involved straight away as he laid the ball off to Wallace to send a long-range effort wide and then after the substitute had showed smart thinking to whip the ball away from Henderson to take a quick corner, David Edgar headed wide as the Clarets tried to build some momentum.
Austin was sent on with 16 minutes to go to add further fresh legs and a link-up between the lively Paterson and Austin ended with the latter letting fly with a shot which was deflected for a corner.
But the Clarets never quite clicked in front of goal and even the consolation of a point was denied them in stoppage time when Norris drove forward and located the bottom corner of the net with a skidding left-foot drive to earn Pompey their ground-breaking win.
David Edgar feels the pain of defeat
Burnley: Grant, Trippier, Mee, Duff, Edgar, Bartley, McCann, Wallace, Rodriguez, Vokes (Austin 74), Stanislas (Paterson 59). Subs: Marney, Easton, Stewart.
Portsmouth: Henderson, Ward, Rocha, Pearce, Mullions, Varney (Huseklepp 20), Halford, Mattock, Kitson, Norris, Thorne. Subs: Mokoena, Futacs, Benjani, Ashdown.
Booked: Kitson 23, Mattock 43
Referee: Steve Rushton