PSV, with coach Dick Advocaat and skipper Mark van Bommel making their returns to the Dutch league, got a perfect start when Jeremain Lens opened the scoring after eight minutes following a defensive blunder from Henrico Drost.
But four minutes later an own goal by Wilfred Bouma brought the scores level before Rodney Sneijder, younger brother of Inter Milan's Wesley, put Waalwijk ahead five minutes from the break with a deflected shot.
Sneijder scored again early in the second half to extend Waalwijk's lead but PSV's Tim Matavz pulled a goal back with a fierce header in the 72nd minute before home defender Guy Ramos was sent off six minutes from time.
On Friday, neighbours Willem II Tilburg and NAC Breda shared the points in a 1-1 draw.
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