Leeds' season hit a new low as Stoke secured their first away win of the season in fine style to send John Carver's side into the bottom three.
The excellent Lee Hendrie opened the scoring after seven minutes with a superbly-struck free-kick.
Andy Griffin slammed in a drive before the hour mark and Danny Higginbotham's header made it 3-0 shortly afterwards.
Leeds' Robbie Blake had a penalty saved, before Ricardo Fuller completed the rout with two minutes remaining.
Leeds caretaker boss John Carver:
"I know what my ambitions are but I have to be quite honest and say possibly this ends my chance of getting the manager's job full-time.
"The result doesn't help my cause but I will take it on the chin.
"It was a dreadful day and my first apology is to the fans because we had built their hopes up."
Stoke manager Tony Pulis:
"It was a smashing result against a big club with good players.
"I think we've been in front in six games this season without winning those matches, so it was good to get a victory and a clean sheet.
"I am so pleased with Lee Hendrie. The players have taken to him immensely and he has real quality."
Leeds: Sullivan, Kelly, Butler, Kilgallon, Wright, Douglas, Westlake (Stone 59), Derry, Lewis, Healy (Blake 59), Horsfield (Cresswell 26).
Subs Not Used: Warner, Foxe.
Booked: Kilgallon, Westlake, Cresswell.
Stoke: Simonsen, Hoefkens, Duberry, Higginbotham, Griffin, Hendrie (Chadwick 85), Russell, Diao (Brammer 82), Delap, Pericard (Fuller 66), Sidibe.
Subs Not Used: Bangoura, Wilkinson.
Booked: Fuller.
Goals: Hendrie 7, Griffin 58, Higginbotham 62, Fuller 88.
Att: 18,173
Ref: T Kettle (Berkshire).