After eight consecutive wins PSV had moved to within six points of leaders Ajax but they fell to their first defeat since early February as Tjaronn Chery netted the winning goal.
Memphis Depay gave PSV the ideal start as he opened the scoring in the third minute but Richairo Zivkovic, who will sign for Ajax next season, levelled after 18 minutes with a close-range finish.
The visitors went ahead just two minutes later as Filip Kostic took advantage of a mistake by Karim Rekik, the defender losing control of the ball and allowing the forward to fire under Jeroen Zoet.
PSV levelled when Jurgen Locadia netted from the penalty spot but Chery sealed the triumph with a 64th-minute free-kick.
To complete a great day for Ajax their other title rivals Vitesse also failed to win, with Peter Bosz's men drawing 2-2 against Heerenveen.
Mike Havenaar gave Vitesse the lead after 31 minutes, only for Alfred Finnbogason to level five minutes before the break – taking him past last season's tally of 24 league goals.
Heerenveen then took the lead just before the hour as Bilal Basacikoglu headed home his fourth league goal of the season from a left wing cross, but Bertrand Traore's first Vitesse goal saw the points shared.
Elsewhere, two goals in the final 11 minutes saw 10-man Heracles come from a goal down to beat NEC 2-1.
Michael Higdon's 14th goal of the season, his fifth in as many games, had put second-bottom NEC ahead in the 20th minute and a five-game winless run looked set to end.
However, Jason Davidson and Matthew Amoah earned Heracles, who had Mike te Wierik sent off, a second victory in a row.
