A new-look Pompey side suffered defeat in their first Checkatrade Trophy group stage match at a sparsely-populated Huish Park.
In a game that was full of attacking verve, but short on defensive solidity, it was Yeovil who emerged with all three points.
That is despite an impressive hat-trick from Michael Smith, who looked full of confidence leading the line for the Blues.
But a brace from Thomas Eaves, as well as goals from Bevis Mugabi and Izale McLeod, ensured the treble counted for little.
Paul Cook changed the entire side that started the league victory at Exeter at the weekend.
Liam O’Brien was handed his debut between the sticks, while there was a first appearance for Matt Clarke since he made a permanent Blues switch.
But the keeper was almost picking the ball out of his net before the first minute had passed, with McLeod bursting through on goal and firing against the post.
The former Pompey striker had another opportunity soon after and this time fired into the side netting from an acute angle.
It was the Blues who broke the deadlock after eight minutes, however, when the impressive Kal Naismith whipped in a pin-point cross from the left and SMITH rose to convert with a bullet header.
But the lead was short-lived, as Yeovil won a free-kick 35 yards out and Matthew Dolan’s shot was diverted in by Mugabi.
McLeod then had the ball in the back of O’Brien’s net again, although the linesman had long since raised his flag for offside.
It certainly counted just seconds later, though, when Eaves neatly controlled a ball over the top and calmly slotted home.
Pompey were still looking a real threat going forward, but both Gareth Evans and Smith failed to trouble Glovers keeper Jonathan Maddison with headers.
It was a different story at the back, however, as a defence containing three midfielders and someone making their first appearance of the season unsurprisingly struggled.
And McLeod made the most of that by netting against his old side on 27 minutes, playing a neat one-two with Otis Khan before lifting the ball over O’Brien.
Still the goals kept coming and this time it was Pompey who found the target thanks to a fine goal.
Naismith picked out SMITH in the box and the striker brought the ball under control before turning and firing into the bottom corner.
But no sooner had the Blues got themselves back into the game, they conceded a fourth, with Eaves allowed far too much time to burst forward and find the net.
Half Time: Yeovil 4 Pompey 2
The start to the second half was not quite as explosive as the first, although Eaves fired over in his search for a hat-trick.
Evans then collected Ben Tollitt’s low cross at the other end, but was not given the time or space to get a decent shot away.
Eaves may have been denied his treble, but SMITH made sure of the matchball when he rose at the back post to head home a deep cross from Adam May.
Pompey immediately made their first substitution, with Tollitt making way and Conor Chaplin looking to join in the goal spree.
One quick break saw him cynically tugged back by Liam Shephard, earning the Yeovil defender a yellow card.
He then surged forward to join Evans in a counter-attack, only to be forced wide and then curl his eventual shot over.
It was Smith who almost drew the Blues level with his fourth of the evening on 72 minutes, but he could not quite get the ball from under his feet and fired narrowly over.
That was his last involvement, as he was withdrawn for Noel Hunt, receiving warm applause from the small pocket of travelling fans.
There was then a late moment of controversy when Amine Linganzi diverted a corner towards the goal.
Maddison was able to smother the ball, but Pompey were adamant it had crossed the line, only for their appeals to fall on deaf ears.
The visitors kept up their attacking intent as they went in search of a leveller, but Yeovil held on for the victory.