Pompey rediscovered their scoring touch but attention soon turned to injuries and refereeing on a night which resulted in Johnstone’s Paint Trophy elimination.
Andy Awford had voiced his criticism of competition rules which restrict wholesale team changes in the build-up for the visit of Northampton.
In the end, injuries during the fixture impacted in a 2-1 Fratton Park defeat, potentially affecting the squad for more than one match.
And the performance of referee Graham Horwood proved just as telling as he left Andy Awford and his staff fuming.
Joe Devera (stomach bug) lasted just eight minutes before he was replaced by Adam Webster, who in turn came off with a leg injury on 60 minutes.
They now join Jack Whatmough (hamstring) and Michael Drennan (calf) on the sidelines, while Ben Chorley is still to return to training.
A worry indeed for manager Awford, whose side did at least manage to net following successive goalless draws.
Ryan Taylor marked his start following a return from injury by converting Alex Wynter’s excellent cross from the right on 36 minutes.
That levelled David Moyo’s 28th-minute opener for the Cobblers in front of a low crowd of 5,853.
Indeed, it was a bright first half from the Blues, who were spurred on by full-debutant Ben Close and the lively Jed Wallace.
After the break, however, the hosts failed to match that attacking threat and substitute Kaid Mohamed converted from close range on 55 minutes to settle the contest for the away side.
Lawson D’Ath’s ugly challenge on Ricky Holmes later sparked furious scenes on the Pompey bench when he received nothing more than a yellow card.
Holmes was also booked for simulation after having a vocal penalty appeal turned down.
And it was Northampton – who also struck the crossbar with a Ryan Cresswell header – who held out to progress through to the next round.
Awford made seven changes for the Trophy visit of the Cobblers, with Paul Jones, Devera, Wallace and Wynter keeping their places from the weekend’s goalless League Two draw at York.
There were recalls for Taylor, Johnny Ertl, Holmes, Nigel Atangana and fit-again Dan Butler in a 4-3-3 system.
Meanwhile, teenagers Nick Awford and Close were given full first-team debuts at Fratton Park.
The bench consisted of another youngster – Bradley Tarbuck – who is back fit after suffering ankle ligament damage in July.
However, for a third successive match there was no place in the squad for loanee Miles Storey.
It took the Blues just 30 seconds to threaten the Northampton goal, when Close threaded an intelligent first-time ball into the path of Wallace.
The midfielder reacted by delivering a low cross in the box.
The ball was agonisingly out of reach of his team-mates, but it was encouraging all the same.
Pompey were forced into a substitution on eight minutes after Devera went down, with physio Sean Duggan indicating the defender couldn’t continue.
That paved the way for an early introduction from the bench for Webster, who slotted into his favoured central-defensive slot.
On 13 minutes, the work-rate of Taylor almost forced the Cobblers defence into a costly slip, following Joel Byrom’s back pass.
Keeper Jordan Archer had to be quick with his clearance, only for it to be charged down by the Blues striker before the ball bounced out for a goal kick.
At the other end, Ertl’s manhandling of Moyo gave the visitors a free-kick down the left, allowing the use of vanishing spray for the first time at Fratton Park.
But the move would come to nothing with a poor delivery from such a promising position.
Cresswell had the ball in Pompey’s net on 17 minutes following a left-wing corner, but it was disallowed by referee Horwood.
However, the Northampton defender had nudged the ball out of the hands of Jones to do so and there was not a murmur of complaint following the match official’s decision.
Then D’Ath’s centre was helped towards goal by Marc Richards, but Jones was once again there to end the danger.
The hosts responded with Wallace putting in a sublime cross from the right and Taylor producing a flying header which flashed just past the upright.
The match was proving to be an entertaining affair early on, and Richards should have broken the deadlock on 21 minutes with a free header from Byrom’s corner.
He was denied, though, by Jones, who conjured up a finger-tip save before smothering the loose ball in a crowded six-yard box.
On 25 minutes, the lively Wallace picked up the ball on the right and cut inside Cresswell, before firing in a left-foot shot which deflected off the chest of Lee Collins for a corner.
Yet it was Northampton who broke the deadlock on 28 minutes through a measured finish from Moyo.
Darren Carter provided the pass through the middle and the striker supplied a right-foot shot which struck the inside of the far post before entering the net.
Awford’s men responded with Wallace having a shot blocked at the near post and then Holmes collecting Atangana’s pull-back before spooning a left-foot shot well wide.
The Blues were level on 36 minutes, though, following an excellent deep cross by Wynter from right-back.
The Crystal Palace loanee picked out Taylor, who took several touches before calmly slotting past Archer for the equaliser.
The striker almost grabbed another just two minutes later, when Butler whipped in a cross from the left and Taylor’s connection was brilliantly turned away at point-blank range by the keeper.
It was an absorbing contest and Moyo managed to head the ball back when it appeared to be running out of play for D’Ath to volley wide from eight-yards out.
Andy Barcham was brought on at the break in place of Wallace. But it was Taylor who almost increased the lead two minutes into the second half with a 25-yarder which fizzed narrowly wide.
Northampton regained the lead in the 55th minute when D’Ath collected a return pass and drilled in a low cross for Mohamed to fire home.
Pompey were dealt a further injury blow on the hour mark when Webster went off with a leg injury, to be replaced by Nicky Shorey.
On 70 minutes, Byrom’s corner was headed against the crossbar by Cresswell as the visitors threatened to put the game out of the hosts’ reach.
Jones came to the Blues’ rescue on 80 minutes when Butler’s short throw back to Wynter was intercepted by Alex Nicholls, whose one-on-one was brilliantly stopped.
There was controversy moments later when D’Ath took down Holmes late on the touchline and – much to the disgust of the home bench – was given just a yellow card.
That moment prompted six minutes of time to be added on, but there was no second equaliser for the Blues as the visitors held on for victory.