A quick-fire double midway through the first half saw Alexander Isak pounce on a Chelsea mistake to put Eddie Howe's side ahead, before an awful moment followed for Axel Disasi, who got his feet tangled up in the six-yard box and put through his own net.
Despite dominating possession, it was Newcastle who had the better chances outside of the goals too, with Joelinton hitting the post early on, Sandro Tonali squandering a decent opportunity just before the second, and Sean Longstaff having a goal ruled out for offside with 15 minutes remaining.
Joao Felix saw a golden opportunity trickle wide mere moments later, but Chelsea struggled to create much in the latter stages, and drew a blank for the first time since the opening day of the season.
Enzo Maresca stuck to his policy of making 11 changes in cup competitions, meaning key man Cole Palmer was left on the bench, and Chelsea struggled in his absence, unlike how they have performed in Europe, and in the previous round against Barrow.
In comparison, Howe picked a strong Newcastle side as they look to end their 56-year wait for a trophy in a competition where they reached the final in 2023.
Isak was joined in attack by the returning Anthony Gordon, while Italy international Tonali also starred in the midfield, helping the Magpies claim a spot in the last eight.
With one fight lost for Chelsea, they still have three more fronts to compete in, and as favourites for the Conference League, that now looks like the most likely route to silverware for the Blues this season.
NEWCASTLE VS. CHELSEA HIGHLIGHTS
Isak goal vs. Chelsea (23rd min, Newcastle 1-0 Chelsea)
Nightmare strikes for Chelsea as they are caught trying to play out from the back, with Renato Veiga put under pressure by Joelinton, Tonali pounces and his tackle falls perfectly for Isak, who sweeps the ball beyond Filip Jorgensen to give Newcastle the lead.
Disasi own goal vs. Chelsea (26th min, Newcastle 2-0 Chelsea)
A disaster for Disasi! Isak's cross is deflected before being flicked on into the six-yard box by Joe Willock, and the Chelsea defender gets his feet in a muddle and scuffs it into his own net in comical fashion as Newcastle go two in front.
MAN OF THE MATCH - SANDRO TONALI
The Italian international looked a class above everyone else in the middle of the pitch, showing fine footwork, the ability to keep the ball moving when necessary, and pressing high up the pitch, which resulted in Newcastle's first goal, and saw Tonali record his first assist for the club.
NEWCASTLE VS. CHELSEA MATCH STATS
Possession: Newcastle 33% - 67% Chelsea
Shots: Newcastle 8 - 17 Chelsea
Shots on target: Newcastle 2 - 3 Chelsea
Corners: Newcastle 1 - 9 Chelsea
Fouls: Newcastle 14 - 15 Chelsea
WHAT NEXT?
Newcastle will revert their attentions to moving back into the top half of the Premier League with a tricky test against Arsenal on Saturday, while Chelsea travel to Old Trafford to face Manchester United in arguably the game of the weekend.