PSV, who had Atiba Hutchinson sent off for a second yellow card after 70 minutes, are top with 50 points from 23 matches ahead of Ajax Amsterdam, Feyenoord and Twente Enschede, who were surprisingly held 1-1 at home by bottom side Willem II Tilburg.
Ajax and Feyenoord, who along with Twente have 44 points, play on Sunday at RKC Waalwijk and PEC Zwolle respectively.
Jacob Mulenga put Utrecht ahead after 10 minutes in Eindhoven when his shot from outside the area was deflected by PSV captain Mark van Bommel and sailed over keeper Boy Waterman.
Mertens equalised in the 29th with a curled free kick over the wall and 20 minutes into the second half Jeremain Lens set up Wijnaldum to seal PSV's win with his 13th goal of the season.
Five minutes later the hosts were reduced to 10 men following a second booking for Hutchinson.
"This was a match with everything in it and one we really had to win," said midfielder Van Bommel, who was shown his ninth yellow card of the season and, along with Hutchinson, will be suspended for next week's clash with Feyenoord.
"We created the chances and deserved the win but they were tough to play with their square midfield that keeps playing football," he told EredivisieLive TV.
Twente have now gone five matches without a win after a last-gasp goal by Ricardo Ippel salvaged a point for lowly Tilburg who cancelled out central defender Douglas's headed opener for Steve McClaren's side two minutes before the break.
In the bottom half of the table, NAC Breda and Heracles Almelo drew 1-1 while Roda JC Kerkrade and visitors AZ Alkmaar finished 2-2 after the home side's Sanharib Malki opened the scoring in the first minute for the third time this season.