An early goal from Reeco Hackett-Fairchild was not enough to keep Pompey in the Carabao Cup, as they suffered a 2-1 defeat at Millwall.
And they had to play almost half the match with just 10 men following Callum Johnson’s red card early in the second half.
It was a fine effort from Hackett-Fairchild that broke the deadlock, but Scott Malone and George Saville netted in quick succession to give the Championship side an interval advantage.
Johnson was then dismissed for a late challenge, although Hackett-Fairchild almost snatched a late leveller for the Blues.
Danny Cowley made three changes from the side that won at Fleetwood in the league at the weekend.
Shaun Williams came in for his competitive debut against his former club, while there were also starts for Johnson and Hackett-Fairchild.
Lee Brown, Kieron Freeman and Marcus Harness all dropped to the bench and Connor Ogilvie reverted to his usual left-back position.
Ex-Fratton favourite Jed Wallace was handed a start by the home side, but Ben Thompson had to be content with a place among the substitutes.
Pompey made a perfect start to the contest, as HACKETT-FAIRCHILD roamed forward and cut onto his left foot before slamming home an unstoppable shot to open his account for the club.
The visiting support had been in fine voice from long before kick-off and that goal only served to whip them into more of a frenzy.
But Millwall grew into the game and started to enjoy more possession before levelling the tie midway through the first half.
Alex Bass got down to deal with an angled drive from Wallace, but Malone reacted quickest to fire the loose ball into the net.
And it soon got worse for the Blues after Sean Raggett had thrown himself into the path of a Tom Bradshaw effort.
The ball was recycled back into the box and Saville was left in far too much space to slot past Bass and turn the match on its head.
It might have got even worse for Pompey just before the break, as Ryan Tunnicliffe played a loose pass inside his own box.
Benik Afone was the grateful recipient of the ball, only for Bass to come to his team-mate’s rescue with a fine stop.
Half Time: Millwall 2 Pompey 1
Cowley made a switch at the break, with Leicester loanee George Hirst leading the line in place of John Marquis.
And there was plenty of controversy once the action got back underway, with Johnson at the centre of it.
First the defender appealed for a penalty when his cross appeared to hit an arm in the area, but referee Charles Breakspear was not interested.
And the official upset the Pompey right-back even more moments later, brandishing a straight red card for a challenge on Bradshaw.
Cowley was forced into another change, with Gassan Ahadme the man to make way for Kieron Freeman.
Williams also made way just past the hour mark and received an ovation from both sets of supporters as he trudged off to be replaced by Michael Jacobs.
The game was drifting, with the Londoners content to keep possession, but the Pompey fans made their own entertainment in the stands.
They serenaded Thompson as he warmed up for the home side and asked for waves from both Cowley brothers.
Millwall had a chance to wrap things up on 76 minutes, with a firm header from substitute Matt Smith coming back off the post.
And Bass then came quickly off his line to narrow the angle for Mahlon Romeo and force the wing-back to shoot wide.
Pompey almost made them pay for their profligacy, as Hackett-Fairchild raced clear on the closing stages.
He eventually managed to squeeze a shot past George Long, only for a well-placed Ryan Leonard to head from the line and ensure the Lions would book their spot in the second round.
Millwall (3-4-1-2): Long; Leonard, Hutchinson (c), Cooper; Romeo, Kieftenbeld, Saville, Malone (Thompson 79); J.Wallace (Mahoney 66); Bradshaw (Smith 66), Afobe
Goals: Malone 21, Saville 27
Subs not used: Bialkowski, Pearce, M.Wallace, Mitchell
Pompey (4-2-3-1): Bass; Johnson, Raggett, Robertson (c), Ogilvie; Tunnicliffe, Williams (Jacobs 61); Hackett-Fairchild, Gassan (Freeman 52), Curtis; Marquis (Hirst 46)
Goals: Hackett-Fairchild 4
Sent off: Johnson
Subs not used: Bazunu, Mnoga, Brown, Harness
Referee: Charles Breakspear
Attendance: 7,915 (2,000 Pompey fans)