The game's only goal came from Adama Traore, his first goal in just under a year, in a solid performance from the Wanderers.
Patrick Cutrone and Morgan Gibbs-White both made their first appearances for the club this season following their loan spells being cut short on a chilly Friday evening.
The defeat means Palace have now lost twice this season at Molineux this season, with both games seeing them lack much-attacking prowess.
Story of the match
Going into the game without a goal in his last four, Fabio Silva should have opened the scoring early on when Pedro Neto's cross fell onto the head of the Portuguese forward.
Unfortunately for Silva, his header looped over the bar despite being left unmarked by the Palace defenders.
Palace then had their first attempt of the evening when Eberechi Eze fired the ball into the stands after Michy Batshuayi picked the midfielder out just inside the penalty area.
Wolves made their possession pay off after 35 minutes when Traore unleashed a thunder left-footed strike past Jack Butland, netting his first goal since finding the net in Espanyol.
The goal was also Traore's first left-footed goal since 2018 and only his sixth career goal with his weaker foot.
Roy Hodgson's side replaced Mamadou Sakho with Cheikhou Kouyate at the break, but the second half started just like the first had ended, with Wolves enjoying the ball more than their opponents.
On his return from injury, Leander Dendoncker nearly doubled the hosts' lead when Traore's blistering pace provided the winger with time to cut the ball back, but the Belgium midfielder was denied by Butland.
Wolves' game management showed signs of improvement to keep Palace quiet for the majority of the evening, keeping Wilfried Zaha quiet when introduced.