The Magpies fell behind midway through the second half but took all three points thanks to the Senegalese striker's late winner after Yohan Cabaye had levelled with a free kick
Jonathan Walters put the visitors ahead from the penalty spot, but that effort was quickly cancelled out by a spectacular free kick from Yohan Cabaye before Cisse clinched the points with a cool finish from close range.
Newcastle named the same team that lost to Swansea last weekend, with Davide Santon, Steven Taylor, Mathieu Debuchy, Cheick Tiote, Yoan Gouffran, Jonas Gutierrez and Cisse all restored to the starting line-up after missing the Europa League clash against Anzhi Makhachkala in midweek.
Stoke meanwhile made just one alteration to the side that lost to West Ham, with Geoff Cameron coming in for Michael Kightly.
After a quiet start, it was Newcastle who began to take control of proceedings, forcing the play with some neat high-tempo passing. Chances were few and far between, however, with Cabaye's long-range effort the best opportunity of the opening stages.
Although it was the hosts that carried the greater threat, Stoke felt they should have been handed a chance to take the lead when they were denied a penalty after Santon looked to have brought down Ryan Shotton just inside the area.
The Magpies were undeterred by that scare, and continued to dictate matters. Asmir Begovic was called into action to make a comfortable stop from Santon's low drive before Gouffran fired over following an excellent long ball from Cabaye.
France international Cabaye was at the heart of most Newcastle attacks, and it was he who went close again with a shot from the edge of the area which was deflected wide of the post.
Despite Newcastle's endeavour, they were unable to break the deadlock before the interval. The half-time stalemate owed much to Stoke's defensive resilience, and the visitors had to be on their guard again as Moussa Sissoko broke through only to hit his shot wide under considerable duress from Begovic.
Alan Pardew's men pushed forward with increasing intent as the half dragged on, but it was the visitors who finally broke the deadlock after Tiote hacked down Walters.
Referee Andre Marriner was left with no option other than to point to the spot and the Irish international duly stepped up and dispatched the resulting spot kick with consummate ease.
It was an advantage that lasted a matter of minutes however, as Newcastle quickly levelled with a superb curling free kick from Cabaye after Begovic had felled Gouffran just outside the penalty area.
The goal gave Newcastle renewed energy, but in spite of the mounting pressure it looked as if the Magpies would be forced to settle for a point.
Cisse, though, would have the final say, latching on to an excellent through ball from Marveaux before lashing past Begovic to push Pardew's side three points closer to survival.