Kinnear, 67, has bore the brunt of the fans' ire since he was brought in to the club by owner Mike Ashley and put in charge of transfer dealings.
The sale of Yohan Cabaye to Paris St Germain and the dismal derby defeat to Sunderland at the weekend appear to have been the final straw.
Manager Alan Pardew, who had not wanted to lose Cabaye, insisted the club had to replace their playmaker if they were to stand any chance of maintaining or improving upon their current standing of eighth. But they were unable to push home their interest in either Lyon's Clement Grenier or Montpellier's Remy Cabella.
Kinnear took up the post in June last year following the departure of Derek Llambias and immediately got on the wrong side of the Magpies' supporters with his inability to pronounce the names of several players correctly in a radio interview with the station TalkSport.
Kinnear pronounced Llambias 'Lambezi' and Cabaye 'Kebab', while Hatem Ben Arfa became 'Afra' during the infamous interview.
A club statement released tonight said: "Newcastle United can confirm that Joe Kinnear has this evening resigned from his position as Director of Football with immediate effect.
The club will be making no further comment."
Kinnear signed a three-year deal when he arrived at St James' Park, an appointment that came four years after he quit the top job through ill health.
At the time Llambias said: "The board are pleased to welcome Joe back to the club. Joe has many years of experience working within the game, and this experience will be of great benefit to the club in achieving our objectives over the coming seasons."
On Saturday, when Newcastle were losing to the Black Cats 3-0 at St James' neither Kinnear nor Ashley were anywhere to be seen.
But both will later have been made aware of the angry outpourings during the game and following the final whistle, with fans demanding a change of regime at the club.
Much of that disatisfaction is down to an inability to bring in signings to make Newcastle a true force in the Premier League.
Something Kinnear, with his self-professed connections, was brought in to do.
"I can open the door to any football manager in the world, anyone," he said, during the TalkSport interview.
"I’ve spent my whole life picking up the phone and talking to Alex Ferguson, week in, week out, what would you do?, what would you do? What would you do?
"I can pick the phone up at any time of the day and speak to Arsene Wenger, I can pick the phone up and speak to any manager in the league in all divisions."
Kinnear certainly wasn't looking to build bridges on his return, saying of the fans who didn't take to him: "I don't know what angle they have got. If they want to sit down and argue with me... Some are talking out of their backsides, a load of tosh.
"I'm not accepting it, as simple as that. I have certainly got more intelligence than them, that's a fact."
Analysing the situation at Newcastle following the derby defeat, The Northern Echo's Scott Wilson wrote: "...it's impossible to know where (Kinnear) has been or what he has been doing in the eight months since he was appointed as the world's only transfer supremo who doesn't complete transfers."
Meanwhile, speaking on Match of the Day 2 this evening, Newcastle legend Alan Shearer, above, said he felt Kinnear's arrival was a strange appointment in the first place.
"I always say nothing should surprise you in football particularly with Newcastle," he said.
"I was surprised in the first place, particularly the way it was announced, when Joe announced it on the radio and got all of those names wrong and had been out of the game for so long.
"When you sell your best player as they did three days before the deadline you have to have a plan and someone ready to come in.
"There was talk about Cabaye going to PSG anyway so there must have been a plan there. Whether that was Newcastle’s way of saying he didn’t do his job or he didn’t bring players in we are not sure.
"I hope it is not ill health, but I am not sure what his job was anyway."
Shearer added: "There is only one guy who can sign the cheques and that is the owner. If Mike does not sign any cheques then the manager and director of football have got their arms tied.
"On Sunday there was no fight, no heart and it was as poor as I have seen for a long time and they were lucky to get away with 3-0
"It was a really nasty atmosphere at St James’ Park and I am sure a lot of that anger was vented at Joe."