The Senegal international secured the three points late on at St James' Park after Romelu Lukaku had cancelled out Demba Ba's first-half opening strike on Sunday afternoon
Newcastle top scorer Demba Ba opened the scoring with a 34th minute volley but Albion hit back through the impressive Romelu Lukaku, whose 55th minute header looked to have ensured that the Baggies take a share of the spoils.
Second-half substitute Cisse stole the points though, deflecting a Sammy Ameobi effort past Ben Foster for the win.
Alan Pardew made nine changes from Thursday night’s 1-0 win over Club Brugge in the Europa League, with only James Perch and Davide Santon retaining their places.
West Brom, meanwhile, made three changes to the side that narrowly lost at home to defending champions Manchester City last weekend. Steve Clarke brought in Zoltan Gera, Peter Odemwingie and more surprisingly, Lukaku, who started in place of top scorer Shane Long.
After a cagey opening, the first real chance of the game came on 11 minutes and should have provided the opening goal. Shola Ameobi swung over a peach of a cross from the right-hand side for Ba to attack but the striker headed over from six yards out.
Ba's missed chance seemed to turn the game in the home side's favour, though, and eight minutes later Santon stung the palms of visiting goalkeeper Foster with a 30-yard effort.
On 25 minutes a quick Albion counter attack almost turned the game on its head. After a Newcastle corner broke down, Graham Dorrans slipped in Lukaku to get a left-footed shot away from just inside the Newcastle box. A fine Tim Krul saved thwarted the big striker to keep the game deadlocked.
Newcastle were in control, though, and Ba opened the scoring minutes later with his seventh league goal of the season. Krul's long pass upfield was flicked on by Shola Ameobi and after a poor attempt at a clearing header from Jonas Olsson, Ba spun round the Swedish international and pounced to volley home.
The goal woke up the visitors and Lukaku should have equalised for West Brom 5 minutes later. The Belgian latched on to Youssuf Mulumbu's superb through ball but was denied again by Krul.
West Brom started the second half as well as they had ended the first and had the ball in the net two minutes after the break. Odemwingie's scuffed effort was helped goalwards by Lukaku, whose slight touch diverted it past Krul only to be correctly ruled out for offside.
On 55 minutes the tireless Lukaku finally got his goal and levelled the game. After some excellent hold-up play, the Belgian striker picked out Gera on the left-hand side before converting his team-mate's cross with a fine header.
Pardew responded to the equaliser by bringing on Cisse and Gabriel Obertan and reverting to a 4-4-2 system. Sammy Ameobi later joined the action after Ba was forced off through injury.
There was still time for some late drama in the north east and after some good advantage play from referee Chris Foy, Sammy Ameobi smashed a 25-yard effort toward goal.
With the ball heading wide of the target it deflected off Cisse, whose touch took it away from Foster and into the net to claim his first Premier League goal of the season and an important three points.