The Potters let slip a one-goal lead given to them by Xherdan Shaqiri shortly before half time, falling to a 19th loss of the campaign to spell the end of their top-flight adventure.
Victory for Palace makes mathematically certain of safety, meanwhile, with James McArthur and Patrick van Aanholt turning the game on its head in the Potteries to keep the Eagles' impressive run of form going.
Palace had plenty of space to run into during large parts of the first half due to Stoke's urgency to find a goal, and Ruben Loftus-Cheek nearly punished the hosts early on when cutting inside and curling a shot over the bar.
If that was not a big enough warning then Wilfried Zaha's dragged shot across goal certainly was, with the Eagles looking the more threatening side.
Stoke slowly started to grow into a stop-start first half, however, coming close through Mame Biram Diouf's glanced header prior to Shaqiri's goal just before the interval.
The Potters' leading scorer took on a free kick from 25 yards out, curling it out of Wayne Hennessey's reach with the aid of a deflection off the wall.
With just an eighth goal in 12-and-a-half matches to their name, Stoke decided against going in search of another and instead sat deeper and deeper.
The visitors were enjoying plenty of the ball and started to turn possession into chances come the hour mark following a low-quality start to the second half.
Palace would go on to punish their opponents 68 minutes in when McArthur slotted the ball past Jack Butland from a slight angle following a swift counter, with Loftus-Cheek claiming the assist.
Zaha then had a big chance to kill Stoke off, only to send the ball high over the crossbar when picked out in acres of space on the penalty spot.
The goal that sent Stoke down arrived late on through Van Aanholt, who made no mistake from a one-on-one position after Ryan Shawcross's attempted interception turned into a perfectly-weighted assist.
STOKE CITY (4-4-2): Butland; Johnson (Campbell 77'), Shawcross, Zouma, Pieters; Bauer, Allen, Ndiaye, Shaqiri; Crouch (Sobhi 67'), Diouf
CRYSTAL PALACE (4-4-2): Hennessey; Ward (Kelly 40'), Tomkins, Sakho, Van Aanholt; Loftus-Cheek, Milivojevic, Cabaye (Benteke 63'), McArthur; Townsend (Schlupp 88'), Zaha