A first half disaster left the Reds with it all to do on Tuesday night, with a second 45 fightback not quite enough to claim a share of the spoils.
Second half goals from Barry Cotter and Callum Styles raised hopes of a stirring comeback with 10 minutes left in this one, but a first half Pompey blitz was enough to see the South Coast side home with all three points.
Inside five minutes, the away side surged up the right flank and a low cross saw Colby Bishop - who looked offside - one-on-one with Liam Roberts, but his shot went wide as both men came together. Referee, Lewis Smith deemed that 'coming together' a foul by the Reds' goalie and awarded Pompey a spot kick.
Up stepped Bishop - who scored in this fixture last term - to send Roberts the wrong way and give his side an early lead.
Within a minute, it was 2-0 to the visitors. The Reds were still aggrieved and lacked concentration, before a clever flick by Bishop saw Paddy Lane through on goal and he finished with aplomb, high into the top corner.
The Reds couldn't find their way into the game, struggling against the high winds with Portsmouth smelling blood. They would grab a third when a cross from the right wing was headed home, unmarked from six yards by Connor Oglivie.
Barnsley looked to be denied by a hand inside the box, but nothing was given, and chances to strike back were few and far between before referee Smith blew for half time.
HALF TIME: Barnsley 0-3 Portsmouth
Neill Collins made three changes during the break, with Sam Cosgrove, Owen Dodgson and Callum Styles introduced and their collective impact was immediate.
A great raid down the left opened up space on the opposite flank which Cosgrove played the ball into for the onrushing Cotter who finished in style, low and under the Pompey stopper.
Devante Cole couldn't add to his eight goals already on this occasion, with him twice going close but first, poking wide from an acute angle before the goalkeeper smothered a second attempt point blank.
Cosgrove nodded just wide at the back post before the man who delivered that cross, another sub in Dodgson this time picked out Styles in a similar area and his header was too hot for the goalie to handle, creeping over the line to set up a barnstorming finish.
But despite a barrage of Reds attacks, a clear opportunity to level was never forthcoming and it ended in defeat for Neill Collins' men, putting a stop to their three-game winning league sequence.
FULL TIME: Barnsley 2-3 Portsmouth
Roberts, Cotter (O'Keeffe), Williams, Łopata, McCart, Cadden (Dodgson), Kane, Russell (Styles), Phillips, Cole (Watters), Cosgrove.
Unused: Killip, Shepherd.
