Barca were off the pace for much of the first half of Tuesday's Group B clash, but Messi broke the deadlock with a trademark free-kick.
They moved through the gears after the restart but found PSV dogged in defence, with two further excellent goals needed to make the points safe.
Ousmane Dembele doubled the lead with an outstanding individual effort and Messi fittingly had the final say, completing his hat-trick by scoring either side of a red card for Samuel Umtiti.
PSV had the better of the opening stages and Gaston Pereiro powered a shot over the bar and Steven Bergwijn curled narrowly wide on the counter with Philippe Coutinho heading over at the other end.
Luis Suarez fired into the side-netting as the hosts struggled to find their rhythm but a surging run forward from Dembele led to the free-kick from which Messi sparked them into life.
Dembele was fouled by Nick Viergever and Messi nonchalantly curled the ball into the top-right corner beyond a helpless Jeroen Zoet.
PSV, to their credit, did not allow the floodgates to open in the immediate aftermath, though a flying Zoet save was required to tip over a curling effort from Coutinho two minutes before the hour mark.
Zoet was beaten all ends up as Suarez dug out a marvellous lob from the edge of the area, only for the Uruguay international to be cruelly denied by the bar.
But Barca's second did eventually come in similarly superb style.
Dembele wonderfully turned two PSV players before running into space and unleashing a right-footed effort that beat the outstretched arm of Zoet, who was soon picking the ball out of his net again, as Barca finished with a flourish.
Ivan Rakitic lifted a delicate ball over the PSV backline that Messi dispatched with a fine first-time finish on the run to make it 3-0 and, after Umtiti received a second yellow for impeding Hirving Lozano, he latched on to a clever Suarez flick and emphatically capped off his treble.
What does it mean: Messi fires early warning to European rivals
Barca have taken a backseat to arch rivals Real Madrid in the Champions League in the last three seasons, last term's stunning loss to Roma marking their third successive quarter-final exit, and for long periods they offered little to suggest a challenge is forthcoming this season. However, Messi took the game by the scruff of the neck in the second half, delivering a reminder, as if one were needed, that this is a team that can put any opponent to the sword.
Pat on the back: Another terrific treble from Messi
Dembele deserves credit for an excellent showing, but Messi's otherworldly numbers speak for themselves. His hat-trick was the 48th of his career and his eighth in the Champions League, more than any other player in the competition's history. He has also now scored more Champions League goals than PSV as a club, scoring 103 to their 102. This was a vintage display from an incredible player who shows no sign of slowing down.
Boot up the backside: Coutinho lacking cutting edge
As Messi and Suarez edge towards the latter stages of their careers, Coutinho will eventually need to take on some of the goalscoring burden, but he was wasteful when opportunities presented themselves and found Zoet in fine form when he did hit the target.
Key Opta stats:
8 - Lionel Messi has scored more hat-tricks than any other player in Champions League/European Cup history. Mesmeric. pic.twitter.com/7kbEUCk8bb— OptaJoe (@OptaJoe) September 18, 2018
- Barcelona have won 25 of their last 27 Champions League games at Camp Nou (W25 D2 L0), with their last defeat there dating back to May 2013 against Bayern Munich (0-3).
- PSV have not won any of their last nine matches in the Champions League (D4 L5).
- Barcelona’s Lionel Messi has scored versus 30 different Champions League sides, only Raul (33) and Cristiano Ronaldo (32) have scored against more different opponents.
- Messi has scored eight direct free-kicks in 2018 - the most he has netted in a calendar year.
Barcelona welcome neighbours Girona to Camp Nou as their attentions turn to maintaining their perfect LaLiga start. PSV's 100 per cent record figures to be more severely challenged as they take on second-placed Ajax in a mouth-watering Eredivisie clash.