Cisse found the net with an injury-time header, having previously spurned a number of glorious opportunities.
The Senegalese forward had been frequently denied by Palace goalkeeper Julian Speroni, but redeemed himself with only his second league goal of the season, giving Newcastle success in their second game with assistant manager John Carver in the dugout in place of the banned Alan Pardew.
Palace, who remain three points above the relegation zone, looked set to claim a share of the spoils after displaying excellent defensive resolve.
The visitors also struck the crossbar through Yannick Bolasie and must have thought they had done enough to earn a point when Cisse missed an open goal late on after Cheick Tiote had crashed an effort against the woodwork.
However, the London club's hopes were dashed at the death as the much-maligned Cisse sealed victory for Newcastle.
Carver named the same XI that started last weekend in a defeat at Fulham, while Cameron Jerome and Jason Puncheon replaced Glenn Murray and Tom Ince for Palace.
Newcastle enjoyed the better of proceedings early on and would have taken the lead after 12 minutes if not for the fine reflexes of Speroni, who reacted well to deny Cisse after he had combined with strike partner Luuk de Jong.
The hosts continued to dictate possession for much of the first half but were frustrated by a well-organised Palace defence.
When Newcastle did carve out another opportunity they were again thwarted by the excellence of Speroni, the Argentinian keeping out Cisse's fine volley from Moussa Sissoko's right-wing cross.
It took until six minutes before the interval for Palace to threaten the Newcastle goal as Bolasie curled narrowly over the bar from the edge of the area.
Paul Dummett then did likewise for Newcastle with a free-kick on the stroke of half-time.
Palace were the brighter of the two sides in the opening stages of the second period and twice came close to claiming the lead.
Kagisho Dikgacoi drew a superb close-range save from Tim Krul and Bolasie clipped the top of the bar with a fine bending effort.
Newcastle brought on Hatem Ben Arfa in place of De Jong in an attempt to turn things around and saw Speroni again save from Cisse following an excellent throughball from Sissoko.
Cisse continued to be at the focal point of almost every Newcastle attack, but spurned another opportunity when he headed over from a Ben Arfa delivery.
It appeared as if his chance at salvation had passed as he failed to connect with Sissoko's pull back after Tiote had seen a deflected strike hit the bar.
Yet there was to be one last twist in the tale as Cisse met Ben Arfa's perfectly placed far-post ball with a bullet header that flew into the top corner.
