Four of the goals - including all of substitute Locadia's efforts - came in the final quarter-of-an-hour to give the scoreline a more lop-sided look than had appeared likely.
Mark van Bommel's deft lob rebounded off the frame of the goal before Mertens emphatically slammed home Ola Toivonen's cross in the 23rd minute and he then curled home a second with the outside of his right foot in the 35th.
VVV's Uche Nwofor, booked for a show of petulance after he appeared to be illegally prevented from shooting in the first half, received a second yellow card in the 65th minute and that, coupled with the introduction of Locadia three minutes later, allowed the visitor to swell the goal tally.
Toivonen set up the Netherlands Under-19 international to mark his Eredivisie debut with a goal and Belgium striker Mertens completed his treble with a solo effort in the 79th minute.
Locadia converted a cross from fellow substitute Wilfred Bouma three minutes later and the 18-year-old rounded off the scoring five minutes from time.
The win leaves PSV three points behind leader FC Twente.
FC Groningen's Michael de Leeuw also netted a hat-trick, including an injury-time winner, to earn his side a 3-2 success against 10-man Roda JC.
De Leeuw tapped in Virgil van Dijk's knockdown in the 17th minute and Roda had Tamas Kadar sent off straight from the restart for a foul denying a goalscoring opportunity.
But it equalised on the stroke of half-time through Mark Jan Fledderus - who himself had been lucky to escape a red card in the early stages.
De Leeuw scored again on 53 minutes but Amin Affane's 20-yard strike 12 minutes from time looked to have earned Ruud Brood's visiting side a point.
Groningen had other ideas, though, and it was De Leeuw again who broke Roda's hearts in the final seconds.
AZ twice let the lead slip before earning a 3-3 draw against RKC Waalwijk with a late equaliser.
Adam Maher brilliantly set up AZ's opener for Viktor Elm, the Sweden midfielder arriving to head home his fourth goal in as many days after a midweek hat-trick against SC Veendam.
Teddy Chevalier brilliantly beat his marker Etienne Reijnen to equalise in the 16th minute but Eredivisie top scorer Jozy Altidore restored AZ's lead in stunning fashion, slaloming through four defenders before firing into the bottom corner.
The lead lasted only three minutes on this occasion, Frank van Mosselveld equalising after Rodney Sneijder's free-kick was blocked.
AZ's recurring weakness from set-pieces reared its head early in the second half as Henrico Drost was left unmarked to head home a corner.
The host had to wait until the 86th minute for the equaliser as Maher, who had earlier been denied by the woodwork, finished after Altidore flicked on substitute Mikhail Rosheuvel's cross.
PEC Zwolle recorded its first win of the season, 1-0 away to Willem II.
Wiljan Plume struck a post in a goalless first half but Zwolle made the breakthrough straight after the interval when Bart van Hintum curled home a free-kick from the edge of the penalty area.
Giovanni Gravenbeek came close to a second against his former club, but home goalkeeper David Meul made an excellent one-handed save.