PSV have 43 points from 20 matches, two more then Twente Enschede who take on fourth-placed Feyenoord (37) on Sunday. Ajax Amsterdam, third with 40, travel to Vitesse Arnhem.
PSV coach Dick Advocaat changed his defence after the 3-1 home defeat by PEC Zwolle last week and his tactical plan paid dividends midway through the first half when a long pass from Kevin Strootman set up Tim Matavz to open the scoring.
Jeremain Lens doubled the lead before the break and 17 minutes into the second half Brazilian Everton pulled one back for Heracles.
Wijnaldum, however, restored the two-goal advantage when he rounded keeper Remko Pasveer and finished with an angled shot before Dries Mertens and Wijnaldum completed the rout.
"After last week this is a welcome win but actually this is a regular win," PSV captain Mark van Bommel told reporters.
"But everything we did wrong last week, too hasty and not concentrated, improved today and if we all play in a compact organisation we can play really well."
Mark Jan Fledderus netted a late rebound after his penalty was saved to salvage a 2-2 draw for Roda JC Kerkrade at ADO Den Haag. Both teams finished with a 10 men after red cards for Vito Wormgoor and Sanharib Malki.
Struggling NAC Breda scored four second-half goals to sink neighbours RKC Waalwijk for their second successive win, while a late header from Denni Avdic earned Zwolle a draw against Marco van Basten's Heerenveen who took the lead through Alfred Finnbogason's 15th goal of the season.