Cisse showed £35million man Andy Carroll how to do it as Newcastle increased their advantage over Liverpool to 11 points.
The Senegal international's 19th-minute header set the Magpies on their way to a victory which leaves them in pole position to claim a top-six Premier League finish, and his second with 59 minutes gone sealed it.
But on a black day for the visitors at St James' Park, keeper Reina was sent off nine minutes from time for head-butting defender James Perch, indicating as he belatedly left the pitch that he would resume their discussion after the final whistle.
Cisse has now scored seven goals in as many games, one fewer than Carroll had managed in 48 appearances for the Merseyside club.
The Gateshead-born frontman's unhappy return ended with 11 minutes left when he was substituted after he had been serenaded with a resounding chorus of: "what a waste of money", while fellow old boy Jose Enrique, who had earlier been taunted over his claims that Newcastle would never again challenge for the top six, spent the final few minutes in goal with manager Kenny Dalglish having used all his substitutes.
But it was all smiles for the locals among a sell-out crowd of 52,363 as Alan Pardew celebrated a repeat of his first game in charge with another win over Liverpool.
The game was billed as a significant showdown in the race for sixth place with the Magpies enjoying an eight-point advantage over the big-spending rivals ahead of kick-off.
It was also a homecoming for Carroll and Enrique, both of whom were treated to a hostile reception by fans who mourned their respective departures, but have since found life without them more than bearable.
Carroll's opening 45 minutes did not go as he would have liked as he became involved in a series of physical tussles after being booked for a blatant ninth-minute dive in an attempt to win a penalty.
His fortunes did not improve when he was presented with his first real chance with 28 minutes.
Another former Magpie, Craig Bellamy, caused problems for makeshift left-back Jonas Gutierrez throughout, and although Mike Williamson managed to get to his cross first, the ball looped up nicely for the striker to get to it before keeper Tim Krul, only for him to loop his header over.
By that point, his side were already trailing as a patched-up Newcastle team defended deep and in numbers, but hit the visitors repeatedly on the break.
Krul had tipped a Bellamy cross on to the bar and full-back Danny Simpson bundled the ball off the line after the Dutchman had spilled Steven Gerrard's cross.
But when the home side broke, they did so at pace, and to great effect after 19 minutes.
Hatem Ben Arfa skipped away from Jay Spearing and then Jonjo Shelvey to send the perfect cross to the far post for Cisse to rise and head past Reina.
For all the Reds continued to enjoy more than their fair share of possession, Newcastle created as many openings, and they might have extended their lead 11 minutes before the break when Demba Ba's long-range shot clipped defender Martin Skrtel and wrong-footed Reina, only to drop just wide.
But Cisse should really have made it 2-0 with four minutes of the half remaining when Danny Guthrie crossed from the right and he sent a downward header past Reina, but wide of the post.
The woodwork came to Liverpool's rescue within three minutes of the restart when Williamson climbed highest to head Guthrie's cross against the foot of the post.
But as the half wore on, it was Liverpool who started to gain the upper hand with their host's carelessness in possession hurting them.
Bellamy only just failed to reach Gerrard's inviting 56th-minute cross and Shelvey drilled the ball straight at Krul.
But when the game's second goal arrived, it did so at the other end, and it was Cisse who again did the damage.
Ba stabbed the ball across goal where Ben Arfa helped it on to Cisse, and he calmly stepped inside Reina before firing home.
Luis Suarez might have reduced the deficit within three minutes but his effort was blocked by Perch.
Dalglish's men continued to fight for salvation as the clock ran down, but their efforts grew increasingly laboured.
Carroll was withdrawn to a chorus of boos and went straight down the tunnel, and Liverpool's hopes were finally dashed when Reina senselessly headbutted Perch nine minutes from time as was sent off.