The Senegal international, who had earlier been denied three times by Palace keeper Julian Speroni, powered substitute Hatem Ben Arfa's cross home in the fourth-minute of stoppage time to snatch a 1-0 win with his first goal since January 4.
Midfielder Cheick Tiote had rattled the crossbar seconds earlier as Palace looked to have survived, but Cisse ensured the Eagles remain firmly entrenched in the battle for Barclays Premier League survival.
Speroni's heroics had kept the Eagles in a game of little real quality until that point, and they might even have been ahead themselves with Yannick Bolasie clipping the crossbar seconds after Kagisho Dikgacoi had gone one-on-one with keeper Tim Krul.
With Alan Pardew watching the game via video-link from the club's training ground and owner Mike Ashley making a rare appearance in the stands, is was assistant manager John Carver who took centre-stage once again, and he headed for the dressing room at the break a frustrated man.
Newcastle largely dominated the opening 45 minutes as Palace receded in numbers in an attempt to deny the hosts time and space, and the ploy proved effective for much of the first half.
Their efforts were aided in no small part by the Magpies' inability to produce enough final balls of genuine quality to stretch them despite the best efforts of Vurnon Anita, the man asked to contribute the invention lost when Yohan Cabaye departed for Paris St Germain in January.
With Loic Remy once again a spectator because of injury - Newcastle have now won none of the seven games he has missed so far this season - it was left to Cisse and Luuk de Jong to lead the attack, and both might have made meaningful impacts.
Cisse was denied by a fine 12th-minute reaction save from Speroni after leaving defender Adrian Mariappa on his backside and thumping in a left-foot shot, with De Jong heading the rebound over.
The Senegal international, who started the game with only one league goal to his name this season, looked certain to add to his tally when he met Mapou Yanga-Mbiwa's inviting 32nd-minute cross with a deft touch, but Speroni was once again equal to the task.
Full-back Paul Dummett came as close as anyone to opening the scoring, but his injury-time free-kick whistled inches over the crossbar.
For their part, Palace attempted to hit Newcastle on the break with the muscular Cameron Jerome causing all kinds of problems for central defensive pairing Fabricio Coloccini and Mike Williamson.
He headed an early Jason Puncheon shot wide and saw a 24th-minute shot blocked by Speroni, but it was midfielder Bolasie who almost blasted the visitors into the lead five minutes before the break when his rising left-foot drive only just cleared the bar.
The Eagles returned in much more positive fashion and went close twice within seconds when Puncheon smashed a blistering left-foot effort wide of the far post and Jerome saw another effort blocked by Yanga-Mbiwa.
With the game opening up, Palace were posing a more regular threat and Krul was called upon for the first time to block Dikgacoi's shot as he ran on to Puncheon's through-ball.
However, the Holland international needed the help of the crossbar seconds later when Bolasie sent in a curling shot from the left side of the penalty area.
It was then that Carver turned to Ben Arfa in the search for fresh inspiration, although it was Moussa Sissoko who fashioned a 62nd-minute opening for Cisse with a powerful run and cross, only for the striker to miskick.
Speroni kept Cisse at bay once again two minutes later with a crucial block after he had pounced on Sissoko's pass, and the striker powered a 70th-minute header just over from Ben Arfa's cross.
Tiote thumped a long-rage 92nd-minute effort against the bar with Cisse failing to turn home Yanga-Mbiwa's cross from the rebound, but he made no mistake when Ben Arfa picked out his run at the death.