Stoke had gone ahead via a penalty just after the hour when Jon Walters ended his personal spot-kick hoodoo and fired home from 12 yards after he had been fouled by Cheick Tiote.
But Newcastle reacted well and within five minutes got the equaliser as Yohan Cabaye brilliantly curled a free-kick into the top corner.
Then with the game heading for a draw, Newcastle claimed the win as Sylvain Marveaux picked out an unmarked Cisse - who fired home from close range.
The win takes Newcastle to 13th in the table, level with Stoke in 11th, and some nine points clear of the drop zone and surely banishes any fears they had they could still be dragged into the relegation dog-fight.
The first half saw both teams striving to get forward, but there was little quality on offer in the final third particularly.
Newcastle had the better of the possession with Moussa Sissoko again impressing in midfield. Jonas Gutierrez and Yohan Cabaye sent efforts just wide, but they failed to trouble Asmir Begovic.
The best chance of the opening half came for the home side just before the break as a ball from Cabaye was not dealt with by Stoke's defence and it came for Yoan Gouffran, but he could only help the ball over from six yards.
Stoke did have an appeal for a foul on Ryan Shotton on the edge of the box as he looked to be caught by Davide Santon as he got by the Italian, but referee Andre Marriner waved play on.
Newcastle started the second half brightly and it was the impressive Sissoko who should have opened the scoring just minutes in as he broke clear courtesy of Tiote's through ball. Begovic raced off his line, but Sissoko could only help it wide of the goal.
Cisse was then seemingly lucky to only be booked as he clashed firstly with Marc Wilson and then Ryan Shawcross, as he took offence to a challenge from the Irishman.
The game then suddenly sprang into life as Stoke went ahead, against the run of play, on the hour. Tiote needlessly dived in on Walters to concede a penalty and despite missing his last two spot-kicks he stepped up and drilled the ball home.
But Newcastle were only behind for five minutes. The marauding Sissoko was brought down on the edge of the box after Glenn Whelan's back pass was intercepted by Gouffran. After a few minutes of squabbling in the box between both sets of players, Cabaye coolly stepped up and curled a brilliant effort into the top corner.
Then with the game heading for a draw, Newcastle claimed the winner as Marveaux found Cisse and he fired the ball past Begovic to give Alan Pardew's men all three points.