Lewis Evans and Adam Jones scored early tries to send the Welsh side on their way at Rodney Parade, while fly-half Jason Tovey kicked the remainder of the points with two conversions, a penalty and a pair of second-half drop-goals.
In reply, Perpigan's scored a last-minute consolation try through Adrien Plante while their Wales international James Hook booted the remaining eight points on what was a disappointing return to his homeland following his recent move to France.
Hook made a great debut for Perpignan against Exeter last week when he scored all of his team's points in a 15-12 victory, but he could not lead his side to victory on Thursday night.
Newport, who beat Cavalieri Prato 33-3 in their opening Pool 4 match, were quickly in charge after scoring two tries in the opening 25 minutes.
Evans charged through a gap to score the first from close range after possession had quickly been fed out towards the left wing, with Tovey adding the conversion.
Good defence then denied Perpignan scrum-half Florian Cazenave a chance near the corner before Jones added Newport's second try when he took possession just ahead of the try-line before touching down unopposed.
Tovey, who had previously kicked a penalty before that score, comfortably converted the try to give Newport a 17-0 lead.
Hook finally got Perpignan on the scoreboard with a penalty just before half-time and he slotted over another at the start of the second period to make it 17-6.
At that point the French side might have sensed a chance to get back into the game, but two Tovey drop-goals restored Newport's 17-point lead and Perpignan suffered another blow midway through the half when Cazenave was sin-binned.
Newport flanker Gavin Thomas was also shown a yellow card with nine minutes remaining, but it made little difference to the final outcome.
Perpignan finished the game with a try as Plante burst through the middle to touch down but it was too little too late, with Hook's subsequent conversion proving the final act of the match.
Meanwhile, Bayonne also remain unbeaten in the competition after sweeping past Bordeaux-Begles 20-3 at Stade Jean Dauger.
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