Utrecht striker Ricky van Wolfswinkel converted two penalties in the opening 15 minutes against Ajax, lifting his season's tally to nine.
Siem de Jong pulled one back for the hosts in stoppage time but could not prevent their first defeat in 26 league matches.
PSV's Brazilian Jonathan Reis broke the deadlock against VVV 11 minutes into the second half when he intercepted a back pass from Jeffrey de Regt and he struck again after Wilfred Bouma had doubled the lead.
They were Reis's first goals for PSV since his return to the club in July after he was sacked in January for refusing to visit a drug rehabilitation centre to undergo treatment for cocaine addiction.
PSV are top with 18 points from eight games, one more than Ajax. Twente Enschede, 4-2 winners over fourth-placed Groningen, have 16 points.
Andreas Granqvist converted a 28th-minute penalty to put Groningen ahead but Bryan Ruiz equalised and then converted a penalty after the break.
Marc Janko headed home Twente's third goal before Tim Matavz pulled one back but Dutch international Theo Janssen settled the match two minutes from time.
