The Catalan giants did not have things all their own way in their Group F opener, but three goals in the final quarter of the game added some garnish to the scoreline.
Ousmane Dembele also netted in between Messi's eighth treble on the European stage, as Spanish champions Barca - reduced to 10 men late on when Samuel Umtiti was red-carded - sent out a real message to the rest of the continent by crushing the reigning Dutch champions.
Heading into the match on the back of a perfect seven-match run that had seen them score 27 goals along the way, PSV were certainly not short of confidence.
Barca took some time to reach full flow in front of a far-from-full Camp Nou, but in Messi and Philippe Coutinho they always looked lively in the opposition half.
Coutinho glanced a header over the bar following some nice link-up play with Messi, who skied an even better chance into the stands at the end of a cutback from his Brazilian teammate from Barca's next chance.
It did not take too long for Messi to reach 61 group-stage goals in the Champions League, though, and it all came through some good play from the direct Dembele to win a free kick for his side 25 yards from goal.
Messi lifted the ball over the wall and out of Jeroen Zoet's reach, keeping Barca on course to maintain their enviable home record in this competition - no points dropped here in the last five editions of the competition.
PSV's run without a win on Spanish goal stood at nine matches ahead of kickoff, and they were fortunate to still be in with a shout of halting that run come the hour mark as Messi had a shot saved and Coutinho squandered a good chance from 12 yards out.
Coutinho then had an effort pushed over the bar by Zoet with another trademark curler, but Hirving Lozano's wayward shot up the other end, and Angelino's sweetly-struck effort on target, offered further reminders that PSV were still in the game.
Without a win of any sort in the Champions League proper in eight matches, the Dutch side took more and more risks as the game entered its final quarter.
Luiz Suarez's inventive shot from the edge of the box hit the PSV crossbar but, just when Barcelona's luck appeared to have run out, two quickfire goals put the game out of reach.
A sublime finish from Dembele, which Zoet had no chance of getting to, gave the hosts some breathing space, and Messi then doubled his personal tally for the night by guiding Rakitic's lofted pass into the bottom corner with a first-time shot.
Despite the margin of his side's lead, Umtiti picked up a second yellow when blocking the path of his opponent, meaning that he will miss the trip to Tottenham Hotspur - defeated late on by Inter Milan tonight - in Barca's next Group B outing.
Three goals became four before full time thanks to Messi's clipped finish over Zoet after being played through by Suarez, maintaining Barca's perfect start and inflicting a first competitive managerial defeat on Mark van Bommel.
BARCELONA (4-3-3): Ter Stegen; Sergi Roberto, Pique, Umtiti, Alba; Rakitic (Vidal 85'), Busquets, Coutinho (Lenglet 81'); Messi, Suarez, Dembele (Arthur 83')
PSV EINDHOVEN (4-3-3): Zoet; Dumfries, Schwaab, Viergever (Isimat-Mirin 67'), Angelino; Hendrix, Rosario (82'), Pereiro; Lozano, Bergwijn (Malen 78'), De Jong