The visiting Reds began the encounter brightly and created numerous chances to break the deadlock.
However, Newcastle goalkeeper Tim Krul was on hand to tip Craig Bellamy's deflected cross onto the bar, while the Dutch international came off his line to force Andy Carroll into heading over from close range.
Carroll, returning to his former club for the first time since his £35m switch in January 2011, went close again in the 15th minute when his headed effort was cleared off the line by Danny Simpson.
In what was their first meaningful effort on goal, Newcastle took the lead. Hatem Ben Arfa's left footed cross found Cisse, who guided a header past Pepe Reina via the aid of the post in the 19th minute.
Cisse had another headed chance late in the half, but his effort skidded wide of the upright.
The hosting Magpies started the second half brightly and struck the woodwork within two minutes of the restart. Mike Williamson rose highest to meet a Danny Guthrie cross, but his powerful effort cannoned back of the post.
Newcastle's second of the afternoon arrived in the 58th minute. Demba Ba squared for Cisse, who rounded Reina before slotting the ball into an unguarded net from six yards out.
Liverpool's response positive and only a block from James Perch prevented Luis Suarez from halving the deficit in the 61st minute.
Carroll's return to Newcastle ended sourly when was substituted by manager Kenny Dalglish with 12 minutes remaining. The England international responded by heading straight down the tunnel.
Moments later the away side were reduced to ten men when goalkeeper Reina was handed his marching orders for a clash with Perch inside the area.
Having used all their permitted substitutions, Liverpool were forced to play the remaining minutes with full-back Jose Enrique in goal.
The Spaniard was not called into action during his stint between the posts as Newcastle held on for a two-goal win.