Newcastle recovered from falling behind early on to beat Southampton in a six-goal thriller at St James' Park.
Alan Pardew's side trailed as early as the third minute when Morgan Schneiderlin beat both Mathieu Debuchy and Steven Taylor in the box to fire past Rob Elliot.
Newcastle then turned the game in their favour just after the half-hour mark as Yoan Gouffran set up influential signing Sissoko to tap home before Cisse's stunning strike put them ahead.
Saints striker Rickie Lambert cooly finished from close range to level just after the interval before a Yohan Cabaye penalty and a Jos Hooiveld own goal sealed the win.
Newcastle had never won a Premier League game after conceding the opening goal but Pardew will be especially pleased to beat the club which sacked him in August 2010.
Crucially for Newcastle, the result means they now go six points clear of the relegation zone and one place and one point above rivals Sunderland.
Southampton were relishing in confidence since their surprisingly comfortable 3-1 win over champions Manchester City a fortnight ago and that confidence was on show in the opening minutes.
A cross into the box was headed over to the feet of Schneiderlin by Lambert and the midfielder did well to shoot past a packed penalty area to make it advantage Southampton.
Newcastle dominated possession since the goal that could have seriously set them back but lacked any cutting edge in the first 30 minutes.
But the home fan's patience was finally rewarded as Gouffran shot at the visiting keeper Boruc but the ball went past him and fell to Sissoko to equalise.
The magpies hit the crossbar before eventually going ahead shortly before half-time.
An Elliot free kick found its way into the visiting half of the pitch and fell to Cisse who with his first touch scored a magnificent strike from 25 yards, leaving Boruc helpless.
Southampton manager Mauricio Pochettino got the start he craved when Lambert came back to haunt the man who signed him at St Marys.
The 31-year old top scorer emerged from a surrounding Newcastle defence and slotted the ball in to make it 2-2.
The home side seemed to have been knocked back by the equaliser and clear-cut chances were few and far between until the game reached 66 minutes.
Right-back Debuchy struck against the arm of left-back and substitute Daniel Fox on the arm from a few yards and Chris Foy made no hesitation in pointing straight to the spot.
Cabaye kept his cool to restore Newcastle's lead and the win was sealed just over 10 minutes from time.
A cross found its way to Fox and ball ping-ponged off him and then Hooiveld and into the back of the net as Newcastle overtake Southampton to go 13th in the Barclays Premier League table.
