The Senegal international struck two minutes into stoppage time to complete a comeback after the Potters had threatened to snatch victory.
Jonathan Walters had given the visitors the lead against the run of play from the penalty spot with 67 minutes gone, but Yohan Cabaye's superb free-kick six minutes later set the stage for Cisse's last-gasp winner.
Rob Elliot had to field a third-minute volley by Peter Crouch. Initially, Newcastle failed to make the most of their possession as Cabaye floated a series of balls into the penalty area which were tailor-made for keeper Asmir Begovic and his defenders.
But Cabaye then sent a 16th-minute shot from distance across Begovic and just past the far post, and Jonas Gutierrez curled another effort similarly wide five minutes later.
Davide Santon tested Begovic with a well-struck 33rd-minute drive, but the home side should really have been in front four minutes later. Cabaye's through-ball took a deflection and evaded Sissoko but it fell nicely for Yoan Gouffran, only for the Frenchman to lift his shot over the bar.
The Magpies were struggling to penetrate a stubborn Stoke defence. Their task grew in size with 23 minutes remaining when, after Cheick Tiote had felled Walters with a rash challenge inside the box, referee Andre Marriner had little option but to point to the spot.
Walters, whose recent record from 12 yards has been dreadful, duly obliged to give the visitors a lead. However, it lasted barely six minutes.
Sissoko was tripped by Whelan literally inches outside the box and Cabaye curled a shot over the wall and in off the underside of the crossbar.
There was even better to come deep into injury time when substitute Sylvain Marveaux picked out Cisse in front of goal and he controlled and fired past the stranded Begovic.