A second half strike from Callum Lang saw Pompey’s unbeaten start to the League One season ended at Wigan.
They had looked in control for long periods of the DW Stadium contest, but did not do enough to test Ben Amos between the sticks.
There had not been much to cause concern from the Latics either, until Lang was left alone to score in the closing stages.
Danny Cowley made three changes from the side that played out a goalless draw at Doncaster the previous week.
Marcus Harness returned from a quad injury to join the forward line, while there were also starts for Lee Brown and Shaun Williams.
Reeco Hackett-Fairchild, Gassan Ahadme and Connor Ogilvie dropped to the bench, where they were joined by recent arrival Louis Thompson.
Former Fratton favourites Jack Whatmough and Tom Naylor were both named in the hosts’ side following their summer switches.
Pompey controlled possession before the break, although there were not many clear-cut openings at either end.
The best for the visiting side came in the early stages, as Sean Raggett met a Williams corner with a downward header that was cleared from the line by Tendayi Darikwa.
Jordan Jones thought he should have won a penalty at the other end after trying to burst through two defenders and tumbling to the turf.
But referee Christopher Sarginson immediately waved the appeals away, much to the chagrin of the home support.
The Blues soon broke threateningly down the right and a delivery from Harness found Ronan Curtis unmarked in the box.
He was able to get a shot away, but it was blocked before it could trouble Amos, who then did the mopping up.
Pompey were passing the ball around nicely and getting into some dangerous positions, without being able to perfect that crucial final pass.
And they almost paid for some dithering at the back just before the break, with a Tom Pearce cross not properly dealt with.
The ball landed kindly at the feet of Darikwa, whose low drilled effort was smothered by Gavin Bazunu.
Half Time: Wigan 0 Pompey 0
Pompey started the second half brightly and Curtis burst forward after winning possession, only to be denied by a fine sliding challenge from former team-mate Naylor.
And then, just a few moments later, it was Whatmough making a key tackle to stop the Republic of Ireland international’s path to goal.
Wigan, meanwhile, were guilty of some sloppy play and a few lapses in concentration allowed the Blues to get forward.
Some patient build-up work eventually saw Kieron Freeman provide a dangerous cross, but Curtis could not keep his header down.
After a spell of Latics pressure, Cowley made a couple of changes in quick succession midway through the second half.
Hackett-Fairchild and George Hirst were the players brought on, with Ryan Tunnicliffe and John Marquis making way.
However, it was a substitute for the home side who started the move that provided a breakthrough on 78 minutes.
James McClean found Pearce and he sent in a low cross from the left that evaded a few players, but found Lang, who calmly slid it into the net.
Pompey immediately set about trying to find an equaliser and Gassan was added to the attacking options.
Wigan held firm, however, to secure all three points and dent the Blues’ promising start to the season.
Wigan (4-2-3-1): Amos; Darikwa (c), Whatmough, Watts, Pearce (Massey 85); Naylor, Cousins; Lang (Edwards 90+4), Keane, Jones (McClean 54); Wyke
Goals: Lang 78
Subs not used: Jones, Aasgaard, Bayliss, Humphrys
Pompey (4-2-3-1): Bazunu; Freeman, Raggett, Robertson (c), Brown; Morrell, Williams; Harness (Gassan 84), Tunnicliffe (Hackett-Fairchild 71), Curtis; Marquis (Hirst 73)
Subs not used: Bass, Ogilvie, Thompson, Jacobs
Referee: Christopher Sarginson
Attendance: 9,571 (963 Pompey fans)