The home side came from a goal down to win the game with late strikes from Jonathan Walters and Cameron Jerome, extending the visitors' losing streak to four
The home side started with an unchanged line-up following their win over Fulham at the weekend, with the game coming too soon for former Newcastle captain Michael Owen's return from injury.
Fabricio Coloccini returned from suspension for the Magpies and replaced his centre-back partner Steven Taylor who, along with Yohan Cabaye, could be out for up to eight weeks.
Newcastle had the first chance of the game after James Perch brushed off a challenge and let fly from distance but his shot was always curling away from Asmir Begovic's goal.
The goalkeeper had to be alert to gather a scuffed left-footed shot from Vurnon Anita as the Magpies were starting to find holes in the Stoke defence early on.
Charlie Adam came the closest to opening the scoring after Davide Santon gave away a free kick. The midfielder's set piece flicked off defender Mike Williamson on to the post and out of play.
This seemed to awaken the Potters and they went close again moments later; this time Glenn Whelan's free kick curled over the bar as Stoke started to turn the screw.
Peter Crouch had to be substituted after a collision with Coloccini left him with blood streaming from his nose and Kenwyne Jones came on to replace him.
It was a quiet first half as both sides battled it out in midfield with Newcastle shading possession, but the match finally opened up after 47 minutes when Newcastle opened the scoring, and it came from goal-shy Papiss Cisse.
Cheikh Tiote dispossessed Glenn Whelan from around 30 yards out before finding Demba Ba. His long-range effort was spilled by Begovic into the path of Cisse who rolled the ball home.
The goal was what the game needed and Jonathan Walters soon went close, beating Santon in the air but heading the ball wide.
Cisse nipped in behind the defence to meet a long ball and sprinted past Robert Huth but could only shoot straight at Begovic.
The game was becoming more and more open at both ends of the pitch, with Walters again beating his man and forces Tim Krul to make a fine diving save on the volley, but he fluffed his lines with the rebound.
Despite the pressure from Stoke looking for an equaliser, it was Newcastle who almost doubled their lead with 15 minutes left.
Another over the top ball found Ba and Begovic had to make a brilliant save to keep the ball out as it was destined for the bottom corner.
The Magpies were set to rue those chances though as Stoke scored two inside five minutes.
The first came on 81 minutes, as Walters got the better of Krul at the third time of asking, planting his header into the top corner out of his reach following a cross from substitute Cameron Jerome.
Three minutes later the hosts were in the lead in typical Stoke fashion. The ball was hit long and into the path of Jones who nodded down for Jerome to smash it past Krul.