Alan Pardew's side - and Cisse especially - had previously spurned a catalogue of chances at St James' Park against a Fulham side who suffered their first defeat in six games.
But with frustration and anxiety growing, the Senegal forward finally beat Mark Schwarzer in the third minute of added-on time for his 11th goal of the season.
After a run of three straight defeats - two in the Barclays Premier League and a 3-1 loss to Benfica on Thursday in the first leg of a Europa League quarter-final tie, this was a crucial win for the Toon.
They dominated in terms of opportunities after Dimitar Berbatov, with four goals in four games coming into this match, had audaciously curled a 20-yard shot just over the right-hand angle of Tim Krul's crossbar and post.
But the win was not without cost because after Steven Taylor had agonisingly planted a header just over the crossbar in running on to a right-wing cross from Moussa Sissoko, Pardew's injury woes increased further.
Already without a host of big names for the run in, the sight of right-back Davide Santon pulling up and clutching the top of his left thigh in the 15th minute will only have intensified Pardew's anxiety.
Beyond that, one sliced clearance from Mapou Yanga-Mbiwa to a low left-wing ball from Damien Duff was the only other serious moment of concern for Pardew and the Magpies through to shortly before the interval.
Instead, going into the break, they should arguably have been in front, only to see three opportunities go begging in the space of six minutes for Cisse either side of the half-hour mark.
Twice Cisse was set up by Sissoko, but on both occasions his right-foot shots were wide, albeit his first much closer than his second as Schwarzer was relieved to see it flash just beyond his left-hand post.
The visitors, though, weathered the storm and countered late on with two chances of their own in a two-minute burst of activity.
From Berbatov's through ball, Bryan Ruiz's angled drive was blocked by Yanga-Mbiwa for a corner eventually swung into the heart of the area by Giorgios Karagounis.
In a melee, Stanislav Manolev was the man who managed to get a boot on the ball inside the six-yard box, but a host of bodies denied him an opener in a half that eventually petered out.
For 20 minutes after the interval, however, it was all Newcastle and another sustained spell where the only thing lacking was a goal.
Initially, Schwarzer was beaten in the 53rd minute via a deflection on to his bar as Emmanuel Frimpong, on minutes earlier for the injured Eyong Enoh, was in the way of a dipping shot from Vurnon Anita, who had earlier replaced Santon.
Five minutes later and again Cisse was guilty of another miss, this time stabbing tamely at a low ball in from Yoan Gouffran that neither Philippe Senderos nor Hangeland could cut out.
After Schwarzer saved an angled drive from Taylor, United then hit the post twice in a matter of seconds, appearing to underline this was simply not going to be their day in front of goal.
From a Sylvain Marveaux corner, Gouffran's initial flick appeared to brush Sascha Riether on the line - potentially even his right arm - on the way to clipping the right-hand upright, with claims for a penalty ignored by referee Kevin Friend.
The rebound fell to Cisse, only for his hapless display to continue in front of goal as from four yards out he sidefooted against the same piece of woodwork.
Proving they were still in the game, Fulham almost stole it in the 68th minute as it took a brilliant fingertip save from Tim Krul to deny Berbatov with a header after he had latched on to a free-kick from John Arne Riise.
Towards the close, Cisse's agonising day continued as a goal-bound header to a right-wing cross from Anita was superbly turned away by Schwarzer in the 88th minute.
But with the clock ticking, Cisse latched on to a loose ball in the area to beat Schwarzer from close range.
His fervent celebrations were understandable as he jumped in among the delirious Newcastle fans, earning himself a booking to boot, but one worthy of his cause.