Yohan Cabaye tucked away a 62nd minute winner, as Newcastle finally won at Old Trafford, after 41 years.
Manchester United were beaten by a late Bryan Oviedo goal on Wednesday and David Moyes demanded for an instant response, as the Magpies visited.
Still, even though Robin Van Persie returned after having injury, its was not enough to inspire the reigning champions, as they looked flat on the day and created few chances.
Debuchy stung De Gea’s palms when he should have scored in the first half and Patric Evra saw his header come off Anita’s arm, but the referee failed to spot it.
Later Sissoko bursted down the right and set up Cabaye to score the winner and even though Van Persie had a goal chalked off for offside, the response from United was not fierce, as they lost at home back-to-back for the first time since 2002.