Hirving Lozano scored a hat-trick for the hosts to help them pile more misery on their crisis-ridden foes, while also extending their perfect start to the league season with a 10th win from a possible 10.
Ajax had gone into half time with a 2-1 lead at Philips Stadion, raising hopes of a victory that would have been diametrically opposed to the two teams' respective form so far this season, but PSV roared back with four unanswered goals in the second half as Ajax suffered yet another humiliation.
The result, coupled with Volendam's win over Excelsior, means that Dutch football's most decorated club with 36 league titles and four European Cups remarkably sit rock-bottom of the Eredivisie table with only five points from their opening eight games.
Having suffered the worst run of form in their entire history heading into Sunday's match, hopes of an Ajax win against a side that had been faultless domestically so far appeared bleak before a ball had even been kicked.
Never before in the storied history of De Topper had the two participants been in such contrasting form, but the early signs suggested that the formbook could be ripped up.
Interim Ajax boss Hedwiges Maduro watched his side go ahead after only 10 minutes when Branco van den Boomen stunned the Philips Stadion into silence.
Lozano restored parity 10 minutes later with his first Eredivisie goal in Eindhoven since February 2019, and while it would not be his last of the afternoon, Ajax did regain the lead courtesy of Brian Bobbey's strike five minutes before half time.
The visitors could have been forgiven for feeling that there may be light at the end of the tunnel as they went into the break ahead after a first half that had seen 26 shots from the two teams combined - the most in any Eredivisie first half since 2017 - but that light was quickly extinguished as PSV equalised and then took the lead within eight minutes of the restart.
First, Luuk de Jong became the latest scourge of Ajax's nightmare season when he netted for a sixth successive Eredivisie match against the Amsterdam outfit - the first player in the competition's history to achieve that.
Just four minutes after that, Ismael Saibari completed the quickfire PSV turnaround, and the second half was only 15 minutes old by the time the hosts had turned that 2-1 deficit into a 4-2 lead through Lozano's second.
Fittingly, it was Lozano who capped off the scoring by completing his hat-trick 18 minutes from time, becoming the first player to net a treble against Ajax in an Eredivisie match since Mark van Bommel 2005.
The 2004-05 campaign was also the last time PSV had beaten Ajax three times in a row prior to Sunday, while Ajax have now suffered five Eredivisie defeats on the bounce for the first time in their entire history.
At the other end of the spectrum, PSV's perfect league campaign so far leaves them five points clear of AZ Alkmaar and FC Twente at the top of the table.