The Geordies recorded their first win at the West London venue since 1986 to give Alan Pardew his first victory as Newcastle manager in London.
Senegal ace Cisse was the star of the show with two contenders for goal of the season which sunk the Blues and dashed their hopes of a top-four finish, meaning they will have to win the Champions League final against Bayern Munich on May 19 if they want to play in Europe's premier club competition next season.
The opening goal came in the 19th minute when Davide Santon made a powerful run down the right flank before finding Cisse on the edge of the area who popped it up with his right foot and then finishing sublimely with a volley past Petr Cech with his left.
Chelsea pushed extremely hard in the second half and looked like pinching a leveller until Cisse scored an absolutely ridiculous goal with the outside of his right foot in injury time. A long throw in bounced down off the chest of Shola Ameobi for the former Freiburg ace, who saw Cech slightly off his line, and produced an audacious curling shot from the left flank which evaded the Czech gloveman and went in just inside the far upright for his 13th goal in 12 outings since arriving in the North East.
After Newcastle's opener, Chelsea had a great chance to level in the 38th minute when Florent Malouda flashed his header wide from a Fernando Torres cross from the right when he really should have scored.
Blues skipper John Terry was desperately unlucky when his header from an 88th-minute corner was goalbound until Santon cleared off the line at the back post and it seemed as though Roberto Di Matteo's men would be able to grab an equaliser especially with 10 minutes of injury time following a nasty collision involving Cheick Tiote and John Obi Mikel which saw the Magpies midfielder needing a stretcher off the pitch.
That time allowed Cisse to again work his magic which saw Newcastle grab maximum points to bounce back from their 4-0 loss at Wigan Athletic on the weekend to join Tottenham on 65 points, just one behind third-placed Arsenal.
For Chelsea, it was just their second loss in 17 since Di Matteo replaced Andre Villas-Boas and they will now look to respond to that defeat with a big performance in Saturday's FA Cup final against Liverpool.
Stamford Bridge, London - 41,559