The 67-year-old was appointed to the position in June last year, but his time in the role has been full of controversy.
Kinnear failed to make a first-team signing in the off-season, bringing in Loic Remy on loan from Queens Park Rangers and 16-year-old Olivier Kemen.
Adding to that, he said no player would leave in January, only for star midfielder Yohan Cabaye to make a £20 million move to Paris Saint-Germain.
Kinnear could only bring in Luuk de Jong from Borussia Monchengladbach on loan.
That followed a bizarre radio interview just days after his appointment when he mispronounced several players' names.
"Newcastle United can confirm that Joe Kinnear has this evening resigned from his position as director of football with immediate effect," the English Premier League club said in a statement.
"The club will be making no further comment."
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