Second-half goals from Mohammed Diame and Nikica Jelavic ended Neil Warnock's unbeaten start as Palace manager since his return in August as Hull City ran out comfortable winners at the KC Stadium.
After a quiet first-half, the Tigers roared into life after the break and Diame's header on the hour mark gave them the advantage, but with Palace pressing for an equaliser Jelavic found a second after Steve Bruce's side counter-attacked a stretched Eagles side, and end the visitors' four game unbeaten league run.
Just 60 seconds had passed when the hosts created a great chance to snatch an early lead. Ahmed Elmohamady found space to push into on the right and sent in a deep cross for Nikica Jelavic but the striker headed over when well-placed to hit the target.
Playing against his former club, Fraizer Campbell was soon in action at the other end when he won a free-kick right on the edge of the Hull box, and Mile Jedinak was a whisker away from dispatching it into the Tigers net but his curler flashed over.
However the visitors suffered a blow after 10 minutes when Scott Dann blocked a powerful strike from Tom Huddlestone and stayed down with a suspected knee injury, which led to him being stretched off and replaced by Adrian Mariappa with Martin Kelly filling the centre-back void.
Despite the defensive reshuffle Palace's looked organised at the back, but Hull nearly scored a goal out of nothing when Jelavic played the ball to Andy Robertson and the wing-back's first-time blast from the corner of the area narrowly missed the target.
In the closing stages of the half Steve Bruce's side cranked up the pressure and were fractions away from taking the lead with the best move of the match on 37 minutes. Mohammed Diame held the ball up on the edge of the box before the powerhouse exchanged swift passes with Jelavic but fired wide of the far post, and on the stroke of half-time the Croatian headed a Huddlestone corner wide.
In the stoppage time allocated for Dann's injury, they went even closer when Diame and Abel Hernandez neatly linked up 30 yards from goal and fed Robertson, and his first-time cross was shanked wide by the latter as the hosts ended the opening 45 strongly but without dirtying Speroni's gloves.
Having not forced Harper into a save either during the first-half, Palace looked more dangerous in the opening minutes of the second. Puncheon saw an ambitious long-ranger sail wide before he sent in a corner that Yannick Bolasie headed goalwards but saw it deflected over the crossbar.
But just before the hour mark the Tigers scored with the game's first goal with it's first attempt on target. After the ball was cleared out of the area, the impressive Robertson had time to control it and whip a threatening cross into the box and Diame beat Damien Delaney to the ball to head the ball past the helpless Speroni.
Warnock responded by throwing on striking duo Marouane Chamakh and Dwight Gayle to try and give the Eagles a little bit more of a cutting edge and with 15 minutes to go a stinging blast from Bolasie finally forced Harper into his first save, with the veteran shot-stopper pushing over the winger's 30 yard effort.
The two substitutes then combined to carve out an opportunity for Puncheon, but his left-footed attempt from the edge of the area once again missed its intended mark, and two minutes from time the result was put beyond doubt.
A defence-splitting pass by Jake Livermore found Jelavic in acres of space, and he turned Kelly before sliding the ball past Speroni to seal the victory and condemn Warnock to his first league defeat since his return.
There was nearly a consolation for Damien Delaney when he headed a Bolasie corner on target but Liam Rosenior was on the line to head the ball away and ensure a difficult afternoon for the Eagles didn't finish on a positive note.
Hull City: Harper, Robertson (Rosenior 81), Davies, Dawson, Chester, Elmohamady (Bruce 90), Huddlestone, Diame, Livermore, Hernandez (Ramirez 75), Jelavic. Subs: Jakupovic, Brady, Quinn, Ben Arfa.
Palace: Speroni, Kelly, Dann (Mariappa 12), Delaney, Ward, Jedinak, Ledley, McArthur (Gayle 70), Bolasie, Puncheon, Campbell (Chamakh 64). Subs: Hennessey, Guedioura, Zaha, Doyle.