Luuk De Jong scored his 21st league goal as PSV pulled eight points clear at the top with a 2-0 win over bottom side NAC Breda.
The former Newcastle striker notched for the first time in four league games when tucking away Cody Gakpo's assist just five minutes into the game at the Philips Stadion.
Substitute Donyell Malen found the top corner in the 72nd minute to double PSV's advantage.
Second-placed Ajax will hope any hangovers that followed Tuesday's shock Champions League thrashing of Real Madrid have eased as they look to respond to PSV's win when they host Fortuna Sittard on Sunday.
Elsewhere, Michel Vlap scored twice to fire Heerenveen to a 3-2 triumph at ADO Den Haag.
The 21-year-old from Sneek converted PSV loanee Sam Lammers' pass in the 22nd minute and, after Tomas Necid equalised for the Storks, Vlap steered in a 67th-minute free-kick to restore Heerenveen's lead.
Lammers looked to have wrapped up all three points with a stoppage-time goal for 3-1 but Abdenasser El Khayati's last-gasp converted penalty for Den Haag jangled nerves among the travelling fans.
Willem II also endured an uncertain finale to their clash with De Graafschap, but Alexander Isak's first-half double proved to be enough for the hosts.
The Swede struck twice inside 22 minutes before Bart Straalman replied for the relegation-threatened Super Farmers. Fernando Lewis restored Willem's lead but a successful spot-kick from Youssef El Jebli meant it finished 3-2.
Earlier, Johnatan Opoku's goal on the stroke of half-time, given following a VAR review, was enough to secure VVV Venlo a 1-0 home win over Excelsior that snapped a three-game losing streak.